Intensity-Modulated Radiation Therapy and Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Anaplastic Thyroid Cancer

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ClinicalTrials.gov Identifier: NCT01236547

Recruitment Status : Completed

First Posted : November 7, 2010

Results First Posted : May 14, 2021

Last Update Posted : July 19, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

NRG Oncology

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Thyroid Gland Anaplastic Carcinoma
Interventions	Radiation: Intensity-Modulated Radiation Therapy Drug: Paclitaxel Drug: Pazopanib Hydrochloride Other: Placebo Administration
Enrollment	123

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description	Pre-Intensity-modulated radiation t...	Pre-IMRT pazopanib 600 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description	Pre-Intensity-modulated radiation therapy (IMRT) pazopanib 800 mg oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 400 mg oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT. Post-concurrent pazopanib 800 mg oral daily and paclitaxel 60 mg/m^2 IV weekly, starting 4 weeks after IMRT for 12 weeks if no evidence of disease or until progression or significant toxicity if evidence of disease.	Pre-IMRT pazopanib 600 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Period Title: Overall Study
Started	11	11	12	42	47
Eligible	11	10	11	36	35
Eligible and Started Study Treatment	11	10	11	36	34
Eligible and Response Assessed	0	0	0	23	27
Completed ^[1]	11	10	11	36	35
Not Completed	0	1	1	6	12
Reason Not Completed
Protocol Violation	0	1	1	6	12
[1] Participants contributing data to results are considered to have completed the study

Baseline Characteristics

Arm/Group Title		(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT	Total
Arm/Group Description		Pre-IMRT pazopanib 800 mg oral dail...	Pre-IMRT pazopanib 600 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...	Total of all reporting groups
Arm/Group Description		Pre-IMRT pazopanib 800 mg oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 400 mg oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT. Post-concurrent pazopanib 800 mg oral daily and paclitaxel 60 mg/m^2 IV weekly, starting 4 weeks after IMRT for 12 weeks if no evidence of disease or until progression or significant toxicity if evidence of disease. Intensity-Modulated Radiation Therapy: 33 fractions over 6.5 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 66 Gy	Pre-IMRT pazopanib 600 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Total of all reporting groups
Overall Number of Baseline Participants		11	10	11	36	35	103
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Eligible participants
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	≤ 49	0 0.0%	0 0.0%	0 0.0%	5 13.9%	4 11.4%	9 8.7%
	50-59	3 27.3%	1 10.0%	1 9.1%	5 13.9%	7 20.0%	17 16.5%
	60-69	4 36.4%	5 50.0%	7 63.6%	19 52.8%	14 40.0%	49 47.6%
	≥ 70	4 36.4%	4 40.0%	3 27.3%	7 19.4%	10 28.6%	28 27.2%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	Female	4 36.4%	7 70.0%	4 36.4%	18 50.0%	19 54.3%	52 50.5%
	Male	7 63.6%	3 30.0%	7 63.6%	18 50.0%	16 45.7%	51 49.5%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	Hispanic or Latino	2 18.2%	0 0.0%	1 9.1%	1 2.8%	3 8.6%	7 6.8%
	Not Hispanic or Latino	8 72.7%	10 100.0%	10 90.9%	29 80.6%	24 68.6%	81 78.6%
	Unknown or Not Reported	1 9.1%	0 0.0%	0 0.0%	6 16.7%	8 22.9%	15 14.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	1 2.8%	0 0.0%	1 1.0%
	Asian	2 18.2%	0 0.0%	1 9.1%	2 5.6%	1 2.9%	6 5.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.9%	1 1.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	2 5.6%	2 5.7%	4 3.9%
	White	9 81.8%	10 100.0%	10 90.9%	23 63.9%	25 71.4%	77 74.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	8 22.2%	6 17.1%	14 13.6%
Zubrod Performance Status ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	0	6 54.5%	7 70.0%	7 63.6%	17 47.2%	15 42.9%	52 50.5%
	1	4 36.4%	3 30.0%	4 36.4%	17 47.2%	16 45.7%	44 42.7%
	2	1 9.1%	0 0.0%	0 0.0%	2 5.6%	4 11.4%	7 6.8%
		[1] Measure Description: 0 - Asymptomatic; 1 - Symptomatic but completely ambulatory; 2 - Symptomatic, <50% in bed during the day; 3 - Symptomatic, >50% in bed, but not bedbound; 4 - Bedbound; 5 - Death
Prior surgery for study cancer ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	None	3 27.3%	3 30.0%	4 36.4%	14 38.9%	16 45.7%	40 38.8%
	Total thyroidectomy	6 54.5%	6 60.0%	5 45.5%	15 41.7%	11 31.4%	43 41.7%
	Partial thyroidectomy	2 18.2%	1 10.0%	2 18.2%	7 19.4%	8 22.9%	20 19.4%
		[1] Measure Description: Thyroidectomy is the surgical removal of all or part of the thyroid gland. Total thyroidectomy indicates that the entire thyroid gland was removed and partial thyroidectomy indicates that only part of the thyroid gland was removed.
T stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	T4a	4 36.4%	2 20.0%	1 9.1%	11 30.6%	12 34.3%	30 29.1%
	T4b	7 63.6%	8 80.0%	10 90.9%	25 69.4%	23 65.7%	73 70.9%
		[1] Measure Description: Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. T4a = Intrathyroidal anaplastic carcinoma-surgically resectable. T4b = Extrathyroidal anaplastic carcinoma-surgically unresectable.
N stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	N0	5 45.5%	0 0.0%	1 9.1%	8 22.2%	6 17.1%	20 19.4%
	N1a	0 0.0%	4 40.0%	2 18.2%	10 27.8%	5 14.3%	21 20.4%
	N1b	6 54.5%	6 60.0%	8 72.7%	14 38.9%	23 65.7%	57 55.3%
	NX	0 0.0%	0 0.0%	0 0.0%	4 11.1%	1 2.9%	5 4.9%
		[1] Measure Description: Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. N0 = No regional lymph node metastasis; N1a = Metastasis to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes); N1b = Metastasis to unilateral, bilateral, or contralateral cervical or superior mediastinal lymph nodes; NX = Lymph node status cannot be assessed.
M stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	10 participants	11 participants	36 participants	35 participants	103 participants
	M0	4 36.4%	7 70.0%	4 36.4%	19 52.8%	21 60.0%	55 53.4%
	M1	4 36.4%	3 30.0%	6 54.5%	13 36.1%	13 37.1%	39 37.9%
	Mx	3 27.3%	0 0.0%	1 9.1%	4 11.1%	1 2.9%	9 8.7%
		[1] Measure Description: Distant metastasis stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the spread of the cancer to organs and tissues in other parts of the body. M0 = No distant metastasis; M1 = Distant metastasis; MX = Distant metastasis cannot be assessed.

Outcome Measures

1.Primary Outcome


Title	(Phase II) Overall Survival
Description	Overall survival time is defined as time from randomization to the dat...
Description	Overall survival time is defined as time from randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after all eligible participants were potentially followed for 3 years.
Time Frame	From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

Outcome Measure Data

Analysis Population Description

Eligible participants on phase II arms


Arm/Group Title	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Overall Number of Participants Analyzed	36	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	37.1 (21.1 to 53.2)	29.0 (13.2 to 44.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Phase II) Pazopanib, Paclitaxel, IMRT, (Phase II) Placebo, Paclitaxel, IMRT
	Comments	Assuming hazard ratio (pazopanib/placebo) of 0.625 (1-year 19% vs. 35.4%), 1-sided alpha 0.15, logrank test, 80% power, 1 interim analysis, required 71 deaths in 79 eligible patients (88 allowing 10% ineligible) in original design. The protocol was amended for phase II final analysis to be performed after all phase II eligible participants were potentially followed for 3 years with 1-sided alpha 0.1379, providing 77% power. See Limitations and Caveats
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2831
	Comments	One-sided significance level = 0.1379
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.52 to 1.43
	Estimation Comments	Reference arm = placebo

2.Primary Outcome


Title	(Phase I) Number of Participants With Treatment-related Grade 4 Hemorrhage, Grade 4 Febrile Neutropenia, or Grade 5 Adverse Event (AE), or Discontinuation of Treatment Due to Toxicity [Adverse Events of Concern (AEC)]
Description	Common Terminology Criteria for AEs (version 4.0) grades AE severity f...
Description	Common Terminology Criteria for AEs (version 4.0) grades AE severity from 1=mild to 5=death. Discontinuation of treatment due to toxicity is defined as < 75% of planned radiation therapy delivered. "Treatment-related" = definitely, probably, or possibly related to treatment. A single run-in arm was originally planned, but additional run-in arms were added due to amendments to the protocol regimen unrelated to toxicities. A two-stage design based on the binomial distribution was used in which the 1st stage analyzes the run-in arm and the 2nd stage analyzes run-in and phase II pazopanib arm participants combined. Because there were multiple run-in arms, only the last is used in the 2nd stage analysis. 1st stage: If ≤4 of 9 participants experience AEC, then conclude treatment is safe. 2nd stage: If ≤8 of 24 participants experience AEC, then conclude treatment safe. Otherwise conclude the treatment is too toxic. Summary data is provided here, see AE Module for specific AE data.
Time Frame	From registration to last follow-up. Maximum follow-up for run-in and phase II participants at time of analysis was 7.4 years.

Outcome Measure Data

Analysis Population Description

First nine eligible participants in run-in each arm and first 15 eligible participants in phase II pazopanib arm.


Arm/Group Title	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 800 mg oral dail...	Pre-IMRT pazopanib 600 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...
Arm/Group Description:	Pre-IMRT pazopanib 800 mg oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 400 mg oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT. Post-concurrent pazopanib 800 mg oral daily and paclitaxel 60 mg/m^2 IV weekly, starting 4 weeks after IMRT for 12 weeks if no evidence of disease or until progression or significant toxicity if evidence of disease.	Pre-IMRT pazopanib 600 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT. Intensity-Modulated Radiation Therapy: 33 fractions over 6.5 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 66 Gy
Overall Number of Participants Analyzed	9	9	9	15
Measure Type: Count of Participants Unit of Measure: Participants
	0 0.0%	0 0.0%	2 22.2%	0 0.0%

3.Secondary Outcome


Title	(Phase II) Local-regional Control
Description	Local-regional failure is defined as local-regional relapse/progressio...
Description	Local-regional failure is defined as local-regional relapse/progression in the thyroid bed or regional lymph nodes. Time to local-regional failure is defined as time from randomization to the date of first local-regional recurrence, last known follow-up (censored), or death without local recurrence (competing risk). Failure rates are estimated using the cumulative incidence method. The protocol specifies 6- and 12-month estimates to be reported and for the full distributions of failure times to be compared between the arms. Analysis occurred after all eligible participants were potentially followed for 3 years.
Time Frame	From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years. (Statistical analysis compares full distributions therefore all available follow-up was used.)

Outcome Measure Data

Analysis Population Description

Eligible participants on phase II arms


Arm/Group Title	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Overall Number of Participants Analyzed	36	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
6 months	20.0 (8.6 to 34.8)	27.3 (13.3 to 43.3)
1 year	28.6 (14.6 to 44.3)	33.6 (17.9 to 50.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Phase II) Pazopanib, Paclitaxel, IMRT, (Phase II) Placebo, Paclitaxel, IMRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6880
	Comments	[Not Specified]
	Method	Log Rank
	Comments	One-sided significance level = 0.15

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95% 0.55 to 2.67
	Estimation Comments	Reference arm = placebo

4.Secondary Outcome


Title	(Phase II) Percentage of Participants With Treatment-related Grade 4 Hemorrhage, Grade 4 Febrile Neutropenia, or Grade 5 Adverse Event, or Discontinuation of Treatment Due to Toxicity [Adverse Events of Concern]
Description	Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades ...
Description	Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades adverse event severity from 1=mild to 5=death. Discontinuation of treatment due to toxicity is defined as < 75% of planned radiation therapy delivered. Adverse events rated as definitely, probably, or possibly related to treatment were considered treatment-related. Summary data is provided in this outcome measure.; See Adverse Events Module for specific adverse event data.
Time Frame	From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

Outcome Measure Data

Analysis Population Description

Eligible phase II participants who started study treatment


Arm/Group Title	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Overall Number of Participants Analyzed	36	34
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	2.8 (0.1 to 14.5)	11.8 (3.3 to 27.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Phase II) Pazopanib, Paclitaxel, IMRT, (Phase II) Placebo, Paclitaxel, IMRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1921
	Comments	Two-sided significance level = 0.05
	Method	Fisher Exact
	Comments	[Not Specified]

5.Secondary Outcome


Title	(Phase II) Percentage of Participants With Treatment-related Grade 3 or 4 Adverse Events Other Than Grade 4 Hemorrhage or Grade 4 Febrile Neutropenia [Not Adverse Events of Concern]
Description	Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades ...
Description	Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events rated as definitely, probably, or possibly related to treatment were considered treatment-related. Summary data is provided in this outcome measure.; See Adverse Events Module for specific adverse event data.
Time Frame	From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

Outcome Measure Data

Analysis Population Description

Eligible phase II participants who started study treatment


Arm/Group Title	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Overall Number of Participants Analyzed	36	34
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	86.1 (70.5 to 95.3)	85.3 (68.9 to 95.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Phase II) Pazopanib, Paclitaxel, IMRT, (Phase II) Placebo, Paclitaxel, IMRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	1.00
	Comments	Two-sided significance level = 0.05
	Method	Fisher Exact
	Comments	[Not Specified]

6.Secondary Outcome


Title	(Phase II) Percentage of Participants With Complete or Partial Response of the Primary Site After Chemoradiation Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	Complete Response: Disappearance of all target lesions; Any pathologic...
Description	Complete Response: Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	2-4 weeks after treatment (approximately week 10-14)

Outcome Measure Data

Analysis Population Description

Eligible participants on phase II arms that with response evaluated


Arm/Group Title	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description:	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
Overall Number of Participants Analyzed	23	27
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	30.4 (13.2 to 52.9)	33.3 (16.5 to 54.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Phase II) Pazopanib, Paclitaxel, IMRT, (Phase II) Placebo, Paclitaxel, IMRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	1.00
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	Two-sided significance level = 0.05

Adverse Events

Time Frame	Weekly pre-IMRT and during IMRT, 2 weeks after IMRT, every months for years 1-2, every 6 months for year 3, then annually. Maximum follow-up time was 7.4 years for run-in arms and 4.2 years for phase II arms.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
Arm/Group Description	Pre-IMRT pazopanib 800 mg oral dail...	Pre-IMRT pazopanib 600 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT pazopanib 400 mg suspensio...	Pre-IMRT placebo 400 mg suspension ...
Arm/Group Description	Pre-IMRT pazopanib 800 mg oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 400 mg oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT. Post-concurrent pazopanib 800 mg oral daily and paclitaxel 60 mg/m^2 IV weekly, starting 4 weeks after IMRT for 12 weeks if no evidence of disease or until progression or significant toxicity if evidence of disease.	Pre-IMRT pazopanib 600 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT pazopanib 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent pazopanib 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.	Pre-IMRT placebo 400 mg suspension oral daily and paclitaxel 80 mg/m^2 IV weekly for 2-3 weeks. Concurrent placebo 300 mg suspension oral daily, paclitaxel 50 mg/m^2 IV weekly during 6.5 weeks of IMRT.
All-Cause Mortality
	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/11 (81.82%)	10/10 (100.00%)	11/11 (100.00%)	31/36 (86.11%)	30/34 (88.24%)
Serious Adverse Events Serious Adverse Events
	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/11 (81.82%)	6/10 (60.00%)	8/11 (72.73%)	28/36 (77.78%)	22/34 (64.71%)
Blood and lymphatic system disorders
Anemia ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Febrile neutropenia ^† 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Cardiac disorders
Atrial fibrillation ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Cardiac arrest ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Cardiac disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Heart failure ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Supraventricular tachycardia ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Gastrointestinal disorders
Abdominal pain ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Colitis ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Constipation ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Dysphagia ^† 1	2/11 (18.18%)	4/10 (40.00%)	1/11 (9.09%)	6/36 (16.67%)	2/34 (5.88%)
Esophageal fistula ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Esophageal pain ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Gastrointestinal disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Hemorrhoidal hemorrhage ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Mucositis oral ^† 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	4/34 (11.76%)
Nausea ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	3/34 (8.82%)
Oral hemorrhage ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Oral pain ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Rectal hemorrhage ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Salivary duct inflammation ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Upper gastrointestinal hemorrhage ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Vomiting ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	1/34 (2.94%)
General disorders
Death NOS ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Fever ^* 1	2/11 (18.18%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	2/34 (5.88%)
Neck edema ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Pain ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Immune system disorders
Allergic reaction ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Infections and infestations
Bronchial infection ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Catheter related infection ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Infections and infestations - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	2/34 (5.88%)
Lung infection ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	1/34 (2.94%)
Sepsis ^* 1	0/11 (0.00%)	1/10 (10.00%)	1/11 (9.09%)	3/36 (8.33%)	1/34 (2.94%)
Skin infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Soft tissue infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Upper respiratory infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Injury, poisoning and procedural complications
Dermatitis radiation ^† 1	0/11 (0.00%)	0/10 (0.00%)	3/11 (27.27%)	1/36 (2.78%)	1/34 (2.94%)
Postoperative hemorrhage ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Tracheal hemorrhage ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Tracheal obstruction ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	1/34 (2.94%)
Tracheostomy site bleeding ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Investigations
Alanine aminotransferase increased ^* 1	2/11 (18.18%)	0/10 (0.00%)	2/11 (18.18%)	0/36 (0.00%)	0/34 (0.00%)
Alkaline phosphatase increased ^* 1	2/11 (18.18%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Aspartate aminotransferase increased ^* 1	1/11 (9.09%)	0/10 (0.00%)	2/11 (18.18%)	0/36 (0.00%)	0/34 (0.00%)
Blood bilirubin increased ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Ejection fraction decreased ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Electrocardiogram QT corrected interval prolonged ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Investigations - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Lymphocyte count decreased ^* 1	5/11 (45.45%)	2/10 (20.00%)	3/11 (27.27%)	3/36 (8.33%)	2/34 (5.88%)
Neutrophil count decreased ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Weight loss ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
White blood cell decreased ^* 1	0/11 (0.00%)	1/10 (10.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Metabolism and nutrition disorders
Dehydration ^* 1	0/11 (0.00%)	0/10 (0.00%)	2/11 (18.18%)	4/36 (11.11%)	2/34 (5.88%)
Hypernatremia ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Hypocalcemia ^* 1	2/11 (18.18%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Hypokalemia ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Hyponatremia ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	1/34 (2.94%)
Hypophosphatemia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Metabolism and nutrition disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Neck pain ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	4/36 (11.11%)	3/34 (8.82%)
Nervous system disorders
Dizziness ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Presyncope ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Recurrent laryngeal nerve palsy ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Syncope ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Psychiatric disorders
Confusion ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	3/36 (8.33%)	1/34 (2.94%)
Renal and urinary disorders
Acute kidney injury ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Respiratory, thoracic and mediastinal disorders
Aspiration ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	2/36 (5.56%)	2/34 (5.88%)
Bronchopulmonary hemorrhage ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Cough ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Dyspnea ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	3/36 (8.33%)	3/34 (8.82%)
Hoarseness ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Hypoxia ^* 1	0/11 (0.00%)	1/10 (10.00%)	1/11 (9.09%)	2/36 (5.56%)	1/34 (2.94%)
Laryngeal edema ^† 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Pharyngolaryngeal pain ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Pleural effusion ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Pneumonitis ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Pneumothorax ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Productive cough ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Respiratory failure ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	2/34 (5.88%)
Sore throat ^* 1	3/11 (27.27%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Stridor ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Skin and subcutaneous tissue disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Vascular disorders
Hematoma ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Hypotension ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	2/34 (5.88%)
Thromboembolic event ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	4/36 (11.11%)	1/34 (2.94%)
1 Term from vocabulary, CTCAE (4.0) * Indicates events were collected by non-systematic assessment † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	(Run-in 1) Pazopanib, Paclitaxel, IMRT	(Run-in 2) Pazopanib, Paclitaxil, IMRT	(Run-in 3) Pazopanib, Paclitaxel, IMRT	(Phase II) Pazopanib, Paclitaxel, IMRT	(Phase II) Placebo, Paclitaxel, IMRT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/11 (90.91%)	10/10 (100.00%)	11/11 (100.00%)	36/36 (100.00%)	33/34 (97.06%)
Blood and lymphatic system disorders
Anemia ^* 1	8/11 (72.73%)	6/10 (60.00%)	6/11 (54.55%)	15/36 (41.67%)	13/34 (38.24%)
Febrile neutropenia ^† 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Cardiac disorders
Sinus bradycardia ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Sinus tachycardia ^* 1	2/11 (18.18%)	1/10 (10.00%)	1/11 (9.09%)	1/36 (2.78%)	4/34 (11.76%)
Ventricular arrhythmia ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Endocrine disorders
Endocrine disorders - Other ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Hypothyroidism ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	4/36 (11.11%)	1/34 (2.94%)
Eye disorders
Blurred vision ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Gastrointestinal disorders
Abdominal pain ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Constipation ^* 1	4/11 (36.36%)	3/10 (30.00%)	3/11 (27.27%)	8/36 (22.22%)	10/34 (29.41%)
Diarrhea ^* 1	8/11 (72.73%)	5/10 (50.00%)	0/11 (0.00%)	16/36 (44.44%)	6/34 (17.65%)
Dry mouth ^† 1	5/11 (45.45%)	8/10 (80.00%)	5/11 (45.45%)	17/36 (47.22%)	15/34 (44.12%)
Dyspepsia ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	4/34 (11.76%)
Dysphagia ^† 1	9/11 (81.82%)	7/10 (70.00%)	10/11 (90.91%)	28/36 (77.78%)	24/34 (70.59%)
Esophageal obstruction ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Esophageal pain ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Esophageal stenosis ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Esophagitis ^* 1	0/11 (0.00%)	2/10 (20.00%)	1/11 (9.09%)	3/36 (8.33%)	2/34 (5.88%)
Gastroesophageal reflux disease ^* 1	2/11 (18.18%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Gastrointestinal disorders - Other ^* 1	2/11 (18.18%)	0/10 (0.00%)	1/11 (9.09%)	8/36 (22.22%)	1/34 (2.94%)
Hemorrhoidal hemorrhage ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Mucositis oral ^† 1	6/11 (54.55%)	7/10 (70.00%)	7/11 (63.64%)	18/36 (50.00%)	16/34 (47.06%)
Nausea ^* 1	6/11 (54.55%)	7/10 (70.00%)	6/11 (54.55%)	20/36 (55.56%)	22/34 (64.71%)
Oral dysesthesia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Oral pain ^* 1	0/11 (0.00%)	1/10 (10.00%)	1/11 (9.09%)	4/36 (11.11%)	5/34 (14.71%)
Rectal hemorrhage ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Salivary duct inflammation ^* 1	1/11 (9.09%)	0/10 (0.00%)	2/11 (18.18%)	3/36 (8.33%)	3/34 (8.82%)
Vomiting ^* 1	5/11 (45.45%)	4/10 (40.00%)	3/11 (27.27%)	10/36 (27.78%)	13/34 (38.24%)
General disorders
Chills ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Edema limbs ^* 1	0/11 (0.00%)	2/10 (20.00%)	0/11 (0.00%)	4/36 (11.11%)	2/34 (5.88%)
Fatigue ^* 1	10/11 (90.91%)	9/10 (90.00%)	9/11 (81.82%)	26/36 (72.22%)	24/34 (70.59%)
Fever ^* 1	5/11 (45.45%)	0/10 (0.00%)	3/11 (27.27%)	3/36 (8.33%)	5/34 (14.71%)
Gait disturbance ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
General disorders and administration site conditions - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	8/36 (22.22%)	2/34 (5.88%)
Infusion related reaction ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	2/34 (5.88%)
Localized edema ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Neck edema ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Non-cardiac chest pain ^* 1	2/11 (18.18%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Pain ^* 1	2/11 (18.18%)	2/10 (20.00%)	1/11 (9.09%)	6/36 (16.67%)	10/34 (29.41%)
Hepatobiliary disorders
Hepatobiliary disorders - Other ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Immune system disorders
Allergic reaction ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	2/34 (5.88%)
Infections and infestations
Catheter related infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Infections and infestations - Other ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Lung infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Mucosal infection ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	2/36 (5.56%)	3/34 (8.82%)
Skin infection ^* 1	1/11 (9.09%)	2/10 (20.00%)	1/11 (9.09%)	2/36 (5.56%)	2/34 (5.88%)
Stoma site infection ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Urinary tract infection ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Wound infection ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Injury, poisoning and procedural complications
Dermatitis radiation ^† 1	7/11 (63.64%)	10/10 (100.00%)	8/11 (72.73%)	22/36 (61.11%)	26/34 (76.47%)
Injury, poisoning and procedural complications - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Investigations
Alanine aminotransferase increased ^* 1	6/11 (54.55%)	8/10 (80.00%)	5/11 (45.45%)	17/36 (47.22%)	3/34 (8.82%)
Alkaline phosphatase increased ^* 1	5/11 (45.45%)	4/10 (40.00%)	1/11 (9.09%)	10/36 (27.78%)	2/34 (5.88%)
Aspartate aminotransferase increased ^* 1	7/11 (63.64%)	7/10 (70.00%)	4/11 (36.36%)	18/36 (50.00%)	4/34 (11.76%)
Blood bilirubin increased ^* 1	5/11 (45.45%)	3/10 (30.00%)	1/11 (9.09%)	8/36 (22.22%)	1/34 (2.94%)
Creatinine increased ^* 1	1/11 (9.09%)	0/10 (0.00%)	2/11 (18.18%)	2/36 (5.56%)	4/34 (11.76%)
Electrocardiogram QT corrected interval prolonged ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
GGT increased ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
INR increased ^* 1	2/11 (18.18%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	2/34 (5.88%)
Investigations - Other ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Lymphocyte count decreased ^* 1	8/11 (72.73%)	1/10 (10.00%)	2/11 (18.18%)	15/36 (41.67%)	12/34 (35.29%)
Neutrophil count decreased ^* 1	4/11 (36.36%)	4/10 (40.00%)	2/11 (18.18%)	13/36 (36.11%)	2/34 (5.88%)
Platelet count decreased ^* 1	6/11 (54.55%)	3/10 (30.00%)	0/11 (0.00%)	9/36 (25.00%)	3/34 (8.82%)
Weight loss ^* 1	6/11 (54.55%)	5/10 (50.00%)	4/11 (36.36%)	10/36 (27.78%)	12/34 (35.29%)
White blood cell decreased ^* 1	8/11 (72.73%)	6/10 (60.00%)	4/11 (36.36%)	17/36 (47.22%)	6/34 (17.65%)
Metabolism and nutrition disorders
Anorexia ^* 1	2/11 (18.18%)	5/10 (50.00%)	3/11 (27.27%)	11/36 (30.56%)	12/34 (35.29%)
Dehydration ^* 1	2/11 (18.18%)	2/10 (20.00%)	3/11 (27.27%)	5/36 (13.89%)	6/34 (17.65%)
Hypercalcemia ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	2/36 (5.56%)	3/34 (8.82%)
Hyperglycemia ^* 1	8/11 (72.73%)	5/10 (50.00%)	3/11 (27.27%)	11/36 (30.56%)	9/34 (26.47%)
Hyperkalemia ^* 1	0/11 (0.00%)	0/10 (0.00%)	3/11 (27.27%)	6/36 (16.67%)	3/34 (8.82%)
Hypermagnesemia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Hypernatremia ^* 1	0/11 (0.00%)	0/10 (0.00%)	3/11 (27.27%)	2/36 (5.56%)	1/34 (2.94%)
Hypoalbuminemia ^* 1	6/11 (54.55%)	6/10 (60.00%)	3/11 (27.27%)	10/36 (27.78%)	8/34 (23.53%)
Hypocalcemia ^* 1	7/11 (63.64%)	6/10 (60.00%)	3/11 (27.27%)	12/36 (33.33%)	9/34 (26.47%)
Hypoglycemia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	3/36 (8.33%)	1/34 (2.94%)
Hypokalemia ^* 1	3/11 (27.27%)	2/10 (20.00%)	1/11 (9.09%)	7/36 (19.44%)	3/34 (8.82%)
Hypomagnesemia ^* 1	2/11 (18.18%)	3/10 (30.00%)	1/11 (9.09%)	4/36 (11.11%)	3/34 (8.82%)
Hyponatremia ^* 1	5/11 (45.45%)	3/10 (30.00%)	2/11 (18.18%)	12/36 (33.33%)	5/34 (14.71%)
Hypophosphatemia ^* 1	4/11 (36.36%)	2/10 (20.00%)	1/11 (9.09%)	4/36 (11.11%)	1/34 (2.94%)
Metabolism and nutrition disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	2/11 (18.18%)	6/36 (16.67%)	3/34 (8.82%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Back pain ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	3/34 (8.82%)
Buttock pain ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Chest wall pain ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Fibrosis deep connective tissue ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Generalized muscle weakness ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Musculoskeletal and connective tissue disorder - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	4/36 (11.11%)	0/34 (0.00%)
Myalgia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Neck pain ^* 1	3/11 (27.27%)	0/10 (0.00%)	2/11 (18.18%)	14/36 (38.89%)	10/34 (29.41%)
Neck soft tissue necrosis ^† 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Pain in extremity ^* 1	2/11 (18.18%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Superficial soft tissue fibrosis ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	1/34 (2.94%)
Trismus ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Nervous system disorders
Dizziness ^* 1	7/11 (63.64%)	1/10 (10.00%)	1/11 (9.09%)	4/36 (11.11%)	2/34 (5.88%)
Dysgeusia ^* 1	3/11 (27.27%)	5/10 (50.00%)	2/11 (18.18%)	14/36 (38.89%)	10/34 (29.41%)
Encephalopathy ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	0/34 (0.00%)
Headache ^* 1	4/11 (36.36%)	2/10 (20.00%)	0/11 (0.00%)	2/36 (5.56%)	5/34 (14.71%)
Hypersomnia ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Memory impairment ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Movements involuntary ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Neuralgia ^† 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	4/34 (11.76%)
Paresthesia ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Peripheral motor neuropathy ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Peripheral sensory neuropathy ^† 1	6/11 (54.55%)	4/10 (40.00%)	2/11 (18.18%)	8/36 (22.22%)	4/34 (11.76%)
Presyncope ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Syncope ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Tremor ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Psychiatric disorders
Agitation ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Anxiety ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	2/36 (5.56%)	9/34 (26.47%)
Confusion ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Depression ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	3/34 (8.82%)
Insomnia ^* 1	2/11 (18.18%)	2/10 (20.00%)	0/11 (0.00%)	1/36 (2.78%)	6/34 (17.65%)
Personality change ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Renal and urinary disorders
Acute kidney injury ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	2/34 (5.88%)
Chronic kidney disease ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	2/34 (5.88%)
Proteinuria ^† 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Renal and urinary disorders - Other ^* 1	2/11 (18.18%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Urinary frequency ^* 1	2/11 (18.18%)	1/10 (10.00%)	0/11 (0.00%)	1/36 (2.78%)	2/34 (5.88%)
Urinary incontinence ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	1/34 (2.94%)
Respiratory, thoracic and mediastinal disorders
Aspiration ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Cough ^* 1	7/11 (63.64%)	1/10 (10.00%)	2/11 (18.18%)	6/36 (16.67%)	9/34 (26.47%)
Dyspnea ^* 1	6/11 (54.55%)	1/10 (10.00%)	1/11 (9.09%)	7/36 (19.44%)	5/34 (14.71%)
Epistaxis ^* 1	4/11 (36.36%)	1/10 (10.00%)	1/11 (9.09%)	2/36 (5.56%)	0/34 (0.00%)
Hiccups ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	1/34 (2.94%)
Hoarseness ^* 1	3/11 (27.27%)	2/10 (20.00%)	4/11 (36.36%)	12/36 (33.33%)	13/34 (38.24%)
Hypoxia ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	1/34 (2.94%)
Laryngeal edema ^† 1	0/11 (0.00%)	1/10 (10.00%)	2/11 (18.18%)	1/36 (2.78%)	2/34 (5.88%)
Laryngeal inflammation ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	2/34 (5.88%)
Laryngeal mucositis ^† 1	1/11 (9.09%)	2/10 (20.00%)	0/11 (0.00%)	0/36 (0.00%)	3/34 (8.82%)
Nasal congestion ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Pharyngeal mucositis ^† 1	1/11 (9.09%)	3/10 (30.00%)	2/11 (18.18%)	5/36 (13.89%)	6/34 (17.65%)
Pharyngolaryngeal pain ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Pleural effusion ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Postnasal drip ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Productive cough ^* 1	3/11 (27.27%)	3/10 (30.00%)	3/11 (27.27%)	2/36 (5.56%)	5/34 (14.71%)
Pulmonary edema ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Respiratory, thoracic and mediastinal disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	5/36 (13.89%)	1/34 (2.94%)
Sore throat ^* 1	5/11 (45.45%)	3/10 (30.00%)	2/11 (18.18%)	3/36 (8.33%)	4/34 (11.76%)
Voice alteration ^* 1	0/11 (0.00%)	2/10 (20.00%)	2/11 (18.18%)	4/36 (11.11%)	1/34 (2.94%)
Wheezing ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia ^* 1	2/11 (18.18%)	7/10 (70.00%)	2/11 (18.18%)	4/36 (11.11%)	3/34 (8.82%)
Dry skin ^* 1	3/11 (27.27%)	1/10 (10.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Pain of skin ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	1/34 (2.94%)
Palmar-plantar erythrodysesthesia syndrome ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	1/36 (2.78%)	0/34 (0.00%)
Pruritus ^* 1	2/11 (18.18%)	2/10 (20.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Rash acneiform ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Rash maculo-papular ^* 1	3/11 (27.27%)	1/10 (10.00%)	0/11 (0.00%)	2/36 (5.56%)	3/34 (8.82%)
Scalp pain ^* 1	0/11 (0.00%)	1/10 (10.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Skin and subcutaneous tissue disorders - Other ^* 1	0/11 (0.00%)	0/10 (0.00%)	1/11 (9.09%)	10/36 (27.78%)	5/34 (14.71%)
Skin hyperpigmentation ^* 1	1/11 (9.09%)	2/10 (20.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Skin hypopigmentation ^* 1	1/11 (9.09%)	1/10 (10.00%)	0/11 (0.00%)	3/36 (8.33%)	0/34 (0.00%)
Skin induration ^† 1	0/11 (0.00%)	3/10 (30.00%)	0/11 (0.00%)	2/36 (5.56%)	1/34 (2.94%)
Skin ulceration ^* 1	1/11 (9.09%)	0/10 (0.00%)	1/11 (9.09%)	0/36 (0.00%)	1/34 (2.94%)
Urticaria ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	0/34 (0.00%)
Vascular disorders
Flushing ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	1/36 (2.78%)	0/34 (0.00%)
Hypertension ^† 1	9/11 (81.82%)	4/10 (40.00%)	6/11 (54.55%)	13/36 (36.11%)	16/34 (47.06%)
Hypotension ^* 1	1/11 (9.09%)	0/10 (0.00%)	0/11 (0.00%)	7/36 (19.44%)	3/34 (8.82%)
Lymphedema ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	2/36 (5.56%)	0/34 (0.00%)
Thromboembolic event ^* 1	0/11 (0.00%)	0/10 (0.00%)	0/11 (0.00%)	0/36 (0.00%)	4/34 (11.76%)
1 Term from vocabulary, CTCAE (4.0) * Indicates events were collected by non-systematic assessment † Indicates events were collected by systematic assessment

Limitations and Caveats

One run-in arm was originally planned; more run-in arms added due to amendments to the protocol regimen unrelated to toxicities. In addition, due to higher than projected rates of ineligibility and consent withdrawals, phase II final analysis was amended to be time-driven (3 years of potential follow-up for all eligible phase II participants) instead of event driven (71 deaths of eligible phase II participants), reducing power from 80% (one-sided alpha 0.15) to 77% (one-sided alpha 0.1379),

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Wendy Seiferheld
Organization:	NRG Oncology
Phone:	215-574-3208
EMail:	seiferheldw@nrgoncology.org

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01236547
Other Study ID Numbers:	NCI-2011-02614 NCI-2011-02614 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000688092 RTOG-0912 ( Other Identifier: NRG Oncology ) RTOG-0912 ( Other Identifier: CTEP ) U10CA180868 ( U.S. NIH Grant/Contract ) U10CA021661 ( U.S. NIH Grant/Contract )
First Submitted:	November 5, 2010
First Posted:	November 7, 2010
Results First Submitted:	March 2, 2021
Results First Posted:	May 14, 2021
Last Update Posted:	July 19, 2022

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