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Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

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ClinicalTrials.gov Identifier: NCT02101788
Recruitment Status : Active, not recruiting
First Posted : April 2, 2014
Results First Posted : September 29, 2020
Last Update Posted : May 3, 2021
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Borderline Ovarian Serous Tumor
Micropapillary Serous Carcinoma
Ovarian Serous Adenocarcinoma
Primary Peritoneal Serous Adenocarcinoma
Recurrent Low Grade Ovarian Serous Adenocarcinoma
Recurrent Primary Peritoneal Serous Adenocarcinoma
Interventions Drug: Letrozole
Drug: Paclitaxel
Drug: Pegylated Liposomal Doxorubicin Hydrochloride
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Drug: Tamoxifen Citrate
Drug: Topotecan
Drug: Trametinib Dimethyl Sulfoxide
Enrollment 260
Recruitment Details A total of 260 patients enrolled before accrual closed on 04/10/2018.
Pre-assignment Details  
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm
Hide Arm/Group Description Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days
Period Title: Overall Study
Started 130 130
Crossover From Arm A to Arm B 88 0
Completed 120 116
Not Completed 10 14
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm Total
Hide Arm/Group Description Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days Total of all reporting groups
Overall Number of Baseline Participants 130 130 260
Hide Baseline Analysis Population Description
All enrolled patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 130 participants 130 participants 260 participants
53.89  (14.03) 53.57  (14.13) 53.7  (14.1)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
20-29 years
9
   6.9%
10
   7.7%
19
   7.3%
30-39 years
18
  13.8%
16
  12.3%
34
  13.1%
40-49 years
21
  16.2%
22
  16.9%
43
  16.5%
50-59 years
28
  21.5%
35
  26.9%
63
  24.2%
60-69 years
39
  30.0%
33
  25.4%
72
  27.7%
>= 70 years
15
  11.5%
14
  10.8%
29
  11.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
Female
130
 100.0%
130
 100.0%
260
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
Hispanic or Latino
7
   5.4%
8
   6.2%
15
   5.8%
Not Hispanic or Latino
118
  90.8%
118
  90.8%
236
  90.8%
Unknown or Not Reported
5
   3.8%
4
   3.1%
9
   3.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.5%
2
   1.5%
4
   1.5%
Native Hawaiian or Other Pacific Islander
2
   1.5%
2
   1.5%
4
   1.5%
Black or African American
5
   3.8%
4
   3.1%
9
   3.5%
White
114
  87.7%
115
  88.5%
229
  88.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
7
   5.4%
7
   5.4%
14
   5.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
United States 102 103 205
United Kingdom 28 27 55
Number of Prior Treatment Regimens  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 130 participants 260 participants
1 Prior Treatment Regimens
30
  23.1%
29
  22.3%
59
  22.7%
2 Prior Treatment Regimens
37
  28.5%
39
  30.0%
76
  29.2%
3 or More Prior Treatment Regimens
63
  48.5%
62
  47.7%
125
  48.1%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the PFS endpoint definition.
Time Frame Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm
Hide Arm/Group Description:
Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days
Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days
Overall Number of Participants Analyzed 130 130
Median (95% Confidence Interval)
Unit of Measure: months
7.2
(5.6 to 9.9)
13.0
(9.9 to 15.0)
2.Secondary Outcome
Title Incidence of Adverse Events (AEs)
Hide Description Number of treated patients with Adverse Events (grade 3 or higher) observed while receiving randomized therapy. Excludes AEs observed among control patients treated with trametinib after crossover.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the AE endpoint definition.
Time Frame During treatment period and up to 100 days after stopping the study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Treated with randomized therapy
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm
Hide Arm/Group Description:
Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days
Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days
Overall Number of Participants Analyzed 127 127
Measure Type: Number
Unit of Measure: participants
Abdominal pain 22 7
Anemia 12 16
Diarrhea 4 13
Fatigue 5 10
Hypertension 6 15
Nausea 14 12
Neutrophil count decreased 1 8
Rash maculo-papular 0 9
Small Intestinal Obstruction 9 16
Vomiting 10 9
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last follow-up were censored on the date of last contact. Patients with disease progression on the Control arm were allowed to cross over to the trametinib arm. Per the protocol, the intent-to-treat OS analysis was not adjusted for crossover.
Time Frame Time from study entry to time of death or date of last contact, an average of 29 months for arm A and 37 months for arm B
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm
Hide Arm/Group Description:
Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days
Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days
Overall Number of Participants Analyzed 130 130
Median (95% Confidence Interval)
Unit of Measure: Months
29.2
(23.5 to 51.6)
37.0 [1] 
(30.3 to NA)
[1]
insufficient number of participants with events
4.Secondary Outcome
Title Objective Tumor Response Rate (Complete Response and Partial Response)
Hide Description The Response Rates were estimated as the binomial proportion of patients with Best Overall Response of Complete or Partial response according to RECIST 1.1 criteria.
Time Frame Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm
Hide Arm/Group Description:
Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days
Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days
Overall Number of Participants Analyzed 130 130
Measure Type: Number
Unit of Measure: participants
8 34
5.Secondary Outcome
Title Patients Reported Acute Quality of Life
Hide Description Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). . The FACT-O TOI score is calculated as the sum of the subscale scores if more than 80% of the FACT-O TOI items provide valid answers and all of the component subscales have valid scores. The FACT-O TOI score ranges 0-100 with a large score suggesting better QOL. Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the quality of life endpoint definition
Time Frame 1. baseline (prior to cycle 1), 12 weeks (prior to cycle 4), 24 weeks (4 weeks post cycle 6), 36 weeks post cycle 1, 52 weeks post cycle 1.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who provided baseline and ≥ 1 follow-up assessment
Arm/Group Title Arm A (Letrozole, Tamoxifen, Paclitaxel, PLD, Topotecan) Arm B (Trametinib)
Hide Arm/Group Description:

Patients receive clinician's choice of either letrozole PO QD on days 1-28, tamoxifen citrate PO BID on days 1-28, paclitaxel IV over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.

Letrozole: Given PO

Paclitaxel: Given IV

Pegylated Liposomal Doxorubicin Hydrochloride: Given IV

Quality-of-Life Assessment: Ancillary studies

Tamoxifen: Given PO

Tamoxifen Citrate: Given PO

Topotecan: Given IV

Topotecan Hydrochloride: Given IV

Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment: Ancillary studies

Trametinib: Given PO

Trametinib Dimethyl Sulfoxide: Given PO

Overall Number of Participants Analyzed 98 100
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 74.5  (16.6) 74.5  (13.7)
12 Weeks 74.2  (16.0) 70.6  (13.5)
24 Weeks 70.2  (15.5) 73.0  (12.8)
36 Weeks 69.3  (18.6) 72.6  (12.8)
52 Weeks 72.1  (16.9) 73.3  (14.3)
6.Secondary Outcome
Title Patient Reported Acute Peripheral Neuropathy Symptoms
Hide Description Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggesting less peripheral neuropathy symptoms
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that provided baseline and ≥ 1 follow-up assessment
Arm/Group Title Arm A (Letrozole, Tamoxifen, Paclitaxel, PLD, Topotecan) Arm B (Trametinib)
Hide Arm/Group Description:

Patients receive clinician's choice of either letrozole PO QD on days 1-28, tamoxifen citrate PO BID on days 1-28, paclitaxel IV over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.

Letrozole: Given PO

Paclitaxel: Given IV

Pegylated Liposomal Doxorubicin Hydrochloride: Given IV

Quality-of-Life Assessment: Ancillary studies

Tamoxifen: Given PO

Tamoxifen Citrate: Given PO

Topotecan: Given IV

Topotecan Hydrochloride: Given IV

Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment: Ancillary studies

Trametinib: Given PO

Trametinib Dimethyl Sulfoxide: Given PO

Overall Number of Participants Analyzed 98 100
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 13.2  (3.5) 12.8  (3.8)
12 Weeks 12.5  (4.0) 12.6  (4.2)
24 Weeks 12.4  (4.0) 12.1  (4.2)
36 Weeks 12.3  (3.8) 12.6  (3.9)
52 Weeks 12.8  (3.2) 12.4  (4.2)
7.Secondary Outcome
Title Markers of Genotype Status Within the MAPK Pathway
Hide Description Will be quantified by whole exome sequencing and will consider the prognostic and predictive abilities of MAPK pathway relative to ORR or PFS. Analysis of the dichotomous markers will be supported by Kaplan Meier plots, and forest plots of the odds-ratio and hazard ratio estimates. Duration of response will be depicted using swimmer plots, with median duration estimated using Kaplan Meier methods. The multivariable models will include covariate adjustment for geographic region, performance status and number of prior regimens, presented using effect coding. The adjusted hazard- and odds- ratio estimates from the multivariable models will be supported by nominal p-values and 2-sided, 95% confidence intervals. Confidence intervals will be interpreted as the plausible range of values for the true (unobserved) ratio that is supported by the data. For the prediction analyses, point estimates and confidence intervals will be provided for the treatment effect within the biomarker levels.
Time Frame Baseline
Outcome Measure Data Not Reported
8.Secondary Outcome
Title pERK Expression
Hide Description Will be quantified using the H-score derived from the immunohistochemistry analysis of patient tumor tissue and is expected to present as a continuous measure. will consider the prognostic and predictive abilities of pERK relative to objective response rate (ORR) or PFS. Analysis of the dichotomous markers will be supported by Kaplan Meier plots, and forest plots of the odds-ratio and hazard ratio estimates. Duration of response will be depicted using swimmer plots, with median duration estimated using Kaplan Meier methods. The multivariable models will include covariate adjustment for geographic region, performance status and number of prior regimens, presented using effect coding. The adjusted hazard- and odds- ratio estimates from the multivariable models will be supported by nominal p-values and 2-sided, 95% confidence intervals. Confidence intervals will be interpreted as the plausible range of values for the true (unobserved) ratio that is supported by the data.
Time Frame Baseline
Outcome Measure Data Not Reported
Time Frame Starting with the first treatment received, and ending 100 days after the last treatment, or at the last following, whichever is sooner. Time frame was approximately 30 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A - Control Arm Arm B - Experimental Arm Crossover From Control to Experimental Arm
Hide Arm/Group Description Investigators choice of Letrozole 2.5 mg po qd continuously, tamoxifen 20mg po bid continuously, paclitaxel 80mg/m2 IV over 1 hr on day 1q 7d, 3 wks on, 1 wk off, Pegylated Liposomal Doxorubicin 40 or 50mg/m2 IV over 1 hr on day 1 q. 28d, Topotecan 4.0mg/m2 over 30 min on day 1,8 and 15 of a 28 day cycle. For each arm, 1 cycle - 28 days Trametinib 2 mg po daily continuous treatment, For each arm, 1 cycle = 28 days Patients randomized to the control arm who crossed over to the experimental arm after disease progression.
All-Cause Mortality
Arm A - Control Arm Arm B - Experimental Arm Crossover From Control to Experimental Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/127 (47.24%)   51/127 (40.16%)   3/88 (3.41%) 
Hide Serious Adverse Events
Arm A - Control Arm Arm B - Experimental Arm Crossover From Control to Experimental Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/127 (33.86%)   45/127 (35.43%)   25/88 (28.41%) 
Blood and lymphatic system disorders       
Anemia * 1  1/127 (0.79%)  4/127 (3.15%)  1/88 (1.14%) 
Cardiac disorders       
Cardiac Arrest * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Eye disorders       
Eye Disorders - Other * 1  2/127 (1.57%)  2/127 (1.57%)  0/88 (0.00%) 
Retinal Vascular Disorder * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Gastrointestinal disorders       
Colonic Obstruction * 1  4/127 (3.15%)  0/127 (0.00%)  5/88 (5.68%) 
Colonic Stenosis * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Colonic Perforation * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Diarrhea * 1  2/127 (1.57%)  1/127 (0.79%)  0/88 (0.00%) 
Vomiting * 1  1/127 (0.79%)  3/127 (2.36%)  1/88 (1.14%) 
Small Intestinal Obstruction * 1  2/127 (1.57%)  11/127 (8.66%)  3/88 (3.41%) 
Abdominal Pain * 1  10/127 (7.87%)  2/127 (1.57%)  2/88 (2.27%) 
Mucositis Oral * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Lower Gastrointestinal Hemorrhage * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Gastrointestinal Disorders - Other * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Nausea * 1  5/127 (3.94%)  1/127 (0.79%)  0/88 (0.00%) 
Ascites * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Jejunal Obstruction * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Obstruction Gastric * 1  0/127 (0.00%)  0/127 (0.00%)  2/88 (2.27%) 
Ileus * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
General disorders       
Pain * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Flu Like Symptoms * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Non-Cardiac Chest Pain * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Edema Limbs * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Death Nos * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Hepatobiliary disorders       
Cholecystitis * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Infections and infestations       
Infections And Infestations - Other * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Upper Respiratory Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Soft Tissue Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Sepsis * 1  1/127 (0.79%)  2/127 (1.57%)  1/88 (1.14%) 
Lung Infection * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Kidney Infection * 1  2/127 (1.57%)  1/127 (0.79%)  0/88 (0.00%) 
Device Related Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Urinary Tract Infection * 1  4/127 (3.15%)  6/127 (4.72%)  2/88 (2.27%) 
Skin Infection * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Lung Infection * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Injury, poisoning and procedural complications       
Intestinal Stoma Obstruction * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Investigations       
Ejection Fraction Decreased * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Neutrophil Count Decreased * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Alkaline Phosphatase Increased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Alanine Aminotransferase Increased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Metabolism and nutrition disorders       
Hyponatremia * 1  2/127 (1.57%)  0/127 (0.00%)  1/88 (1.14%) 
Hypokalemia * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Dehydration * 1  2/127 (1.57%)  0/127 (0.00%)  0/88 (0.00%) 
Anorexia * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hypoalbuminemia * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Psychiatric disorders       
Delirium * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Renal and urinary disorders       
Renal And Urinary Disorders - Other * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Urinary Tract Obstruction * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Hematuria * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Acute Kidney Injury * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Urinary Retention * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Reproductive system and breast disorders       
Vaginal Hemorrhage * 1  3/127 (2.36%)  0/127 (0.00%)  1/88 (1.14%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory Failure * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Pneumonitis * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Pleural Effusion * 1  1/127 (0.79%)  2/127 (1.57%)  2/88 (2.27%) 
Dyspnea * 1  2/127 (1.57%)  2/127 (1.57%)  0/88 (0.00%) 
Chylothorax * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Bronchopulmonary Hemorrhage * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Skin and subcutaneous tissue disorders       
Skin And Subcutaneous Tissue Disorders - Other * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Rash Maculo-Papular * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Vascular disorders       
Thromboembolic Event * 1  1/127 (0.79%)  4/127 (3.15%)  0/88 (0.00%) 
Hypotension * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Hypertension * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A - Control Arm Arm B - Experimental Arm Crossover From Control to Experimental Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   124/127 (97.64%)   127/127 (100.00%)   88/88 (100.00%) 
Blood and lymphatic system disorders       
Thrombotic Thrombocytopenic Purpura * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Lymph Node Pain * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Anemia * 1  54/127 (42.52%)  66/127 (51.97%)  51/88 (57.95%) 
Febrile Neutropenia * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Cardiac disorders       
Atrial Fibrillation * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Ventricular Tachycardia * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Conduction Disorder * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Sinus Bradycardia * 1  0/127 (0.00%)  4/127 (3.15%)  1/88 (1.14%) 
Palpitations * 1  5/127 (3.94%)  5/127 (3.94%)  0/88 (0.00%) 
Left Ventricular Systolic Dysfunction * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Acute Coronary Syndrome * 1  2/127 (1.57%)  0/127 (0.00%)  1/88 (1.14%) 
Pulmonary Valve Disease * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Tricuspid Valve Disease * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Atrioventricular Block First Degree * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Cardiac Disorders - Other * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Pericardial Effusion * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Sinus Tachycardia * 1  2/127 (1.57%)  8/127 (6.30%)  7/88 (7.95%) 
Mitral Valve Disease * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Cardiac Arrest * 1  0/127 (0.00%)  0/127 (0.00%)  2/88 (2.27%) 
Heart Failure * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Chest pain - Cardiac * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Ear and labyrinth disorders       
Middle Ear Inflammation * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Vertigo * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Tinnitus * 1  4/127 (3.15%)  4/127 (3.15%)  1/88 (1.14%) 
Hearing Impaired * 1  2/127 (1.57%)  2/127 (1.57%)  2/88 (2.27%) 
Ear Pain * 1  1/127 (0.79%)  3/127 (2.36%)  2/88 (2.27%) 
Endocrine disorders       
Hypothyroidism * 1  2/127 (1.57%)  0/127 (0.00%)  2/88 (2.27%) 
Hyperparathyroidism * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hyperthyroidism * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Eye disorders       
Eye Disorders - Other * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Watering Eyes * 1  2/127 (1.57%)  3/127 (2.36%)  2/88 (2.27%) 
Keratitis * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Eye Pain * 1  3/127 (2.36%)  1/127 (0.79%)  0/88 (0.00%) 
Cataract * 1  1/127 (0.79%)  0/127 (0.00%)  2/88 (2.27%) 
Photophobia * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Conjunctivitis * 1  0/127 (0.00%)  3/127 (2.36%)  2/88 (2.27%) 
Retinal Tear * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Retinopathy * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Corneal Ulcer * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Retinal Vascular Disorder * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Blurred Vision * 1  12/127 (9.45%)  32/127 (25.20%)  13/88 (14.77%) 
Dry Eye * 1  7/127 (5.51%)  13/127 (10.24%)  11/88 (12.50%) 
Retinal Detachment * 1  0/127 (0.00%)  2/127 (1.57%)  2/88 (2.27%) 
Floaters * 1  0/127 (0.00%)  4/127 (3.15%)  4/88 (4.55%) 
Eyelid Function Disorder * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Flashing lights * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Gastrointestinal disorders       
Dysphagia * 1  3/127 (2.36%)  6/127 (4.72%)  7/88 (7.95%) 
Dyspepsia * 1  8/127 (6.30%)  13/127 (10.24%)  5/88 (5.68%) 
Dry Mouth * 1  5/127 (3.94%)  19/127 (14.96%)  22/88 (25.00%) 
Colonic Obstruction * 1  6/127 (4.72%)  1/127 (0.79%)  7/88 (7.95%) 
Colonic Stenosis * 1  1/127 (0.79%)  1/127 (0.79%)  2/88 (2.27%) 
Colonic Perforation * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Colitis * 1  1/127 (0.79%)  1/127 (0.79%)  2/88 (2.27%) 
Colonic Hemorrhage * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Constipation * 1  49/127 (38.58%)  54/127 (42.52%)  31/88 (35.23%) 
Diarrhea * 1  43/127 (33.86%)  92/127 (72.44%)  53/88 (60.23%) 
Cheilitis * 1  0/127 (0.00%)  2/127 (1.57%)  2/88 (2.27%) 
Vomiting * 1  44/127 (34.65%)  58/127 (45.67%)  33/88 (37.50%) 
Bloating * 1  21/127 (16.54%)  21/127 (16.54%)  18/88 (20.45%) 
Small Intestinal Perforation * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Stomach Pain * 1  1/127 (0.79%)  3/127 (2.36%)  0/88 (0.00%) 
Small Intestinal Obstruction * 1  9/127 (7.09%)  15/127 (11.81%)  9/88 (10.23%) 
Abdominal Pain * 1  60/127 (47.24%)  56/127 (44.09%)  48/88 (54.55%) 
Rectal Hemorrhage * 1  4/127 (3.15%)  3/127 (2.36%)  6/88 (6.82%) 
Oral Dysesthesia * 1  0/127 (0.00%)  2/127 (1.57%)  4/88 (4.55%) 
Mucositis Oral * 1  23/127 (18.11%)  46/127 (36.22%)  24/88 (27.27%) 
Lower Gastrointestinal Hemorrhage * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Oral Hemorrhage * 1  0/127 (0.00%)  2/127 (1.57%)  2/88 (2.27%) 
Ileus * 1  1/127 (0.79%)  0/127 (0.00%)  2/88 (2.27%) 
Gastrointestinal Pain * 1  1/127 (0.79%)  2/127 (1.57%)  1/88 (1.14%) 
Oral Pain * 1  1/127 (0.79%)  5/127 (3.94%)  4/88 (4.55%) 
Abdominal Distension * 1  6/127 (4.72%)  6/127 (4.72%)  5/88 (5.68%) 
Nausea * 1  65/127 (51.18%)  77/127 (60.63%)  48/88 (54.55%) 
Gastroparesis * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Gastroesophageal Reflux Disease * 1  10/127 (7.87%)  11/127 (8.66%)  10/88 (11.36%) 
Rectal Pain * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Gastric Fistula * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Fecal Incontinence * 1  3/127 (2.36%)  1/127 (0.79%)  2/88 (2.27%) 
Hemorrhoidal Hemorrhage * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hemorrhoids * 1  1/127 (0.79%)  4/127 (3.15%)  3/88 (3.41%) 
Ascites * 1  7/127 (5.51%)  5/127 (3.94%)  2/88 (2.27%) 
Toothache * 1  2/127 (1.57%)  1/127 (0.79%)  1/88 (1.14%) 
Jejunal Obstruction * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Anal Fistula * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Dental Caries * 1  1/127 (0.79%)  3/127 (2.36%)  1/88 (1.14%) 
Flatulence * 1  2/127 (1.57%)  4/127 (3.15%)  4/88 (4.55%) 
Gastritis * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Enterocolitis * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Proctitis * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Periodontal disease * 1  0/127 (0.00%)  0/127 (0.00%)  2/88 (2.27%) 
Ileus * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Lip pain * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Esophageal Stenosis * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
General disorders       
Pain * 1  13/127 (10.24%)  25/127 (19.69%)  13/88 (14.77%) 
Neck Edema * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Malaise * 1  0/127 (0.00%)  4/127 (3.15%)  3/88 (3.41%) 
Localized Edema * 1  0/127 (0.00%)  6/127 (4.72%)  7/88 (7.95%) 
Irritability * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Flu Like Symptoms * 1  4/127 (3.15%)  5/127 (3.94%)  1/88 (1.14%) 
Edema Trunk * 1  1/127 (0.79%)  3/127 (2.36%)  1/88 (1.14%) 
Non-Cardiac Chest Pain * 1  6/127 (4.72%)  7/127 (5.51%)  3/88 (3.41%) 
Edema Limbs * 1  15/127 (11.81%)  61/127 (48.03%)  36/88 (40.91%) 
Edema Face * 1  1/127 (0.79%)  10/127 (7.87%)  5/88 (5.68%) 
Fatigue * 1  75/127 (59.06%)  92/127 (72.44%)  59/88 (67.05%) 
Fever * 1  13/127 (10.24%)  22/127 (17.32%)  12/88 (13.64%) 
Chills * 1  3/127 (2.36%)  15/127 (11.81%)  10/88 (11.36%) 
Facial pain * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Infusion related reaction * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Multi-Organ failure * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Hepatobiliary disorders       
Portal Vein Thrombosis * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Cholecystitis * 1  2/127 (1.57%)  0/127 (0.00%)  0/88 (0.00%) 
Immune system disorders       
Allergic Reaction * 1  1/127 (0.79%)  8/127 (6.30%)  0/88 (0.00%) 
Infections and infestations       
Infections And Infestations - Other * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Wound Infection * 1  4/127 (3.15%)  1/127 (0.79%)  0/88 (0.00%) 
Upper Respiratory Infection * 1  6/127 (4.72%)  14/127 (11.02%)  0/88 (0.00%) 
Tooth Infection * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Vulval Infection * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Soft Tissue Infection * 1  2/127 (1.57%)  1/127 (0.79%)  2/88 (2.27%) 
Skin Infection * 1  6/127 (4.72%)  19/127 (14.96%)  10/88 (11.36%) 
Sinusitis * 1  3/127 (2.36%)  7/127 (5.51%)  1/88 (1.14%) 
Sepsis * 1  1/127 (0.79%)  4/127 (3.15%)  3/88 (3.41%) 
Rhinitis Infective * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Rash Pustular * 1  1/127 (0.79%)  4/127 (3.15%)  4/88 (4.55%) 
Pharyngitis * 1  2/127 (1.57%)  0/127 (0.00%)  1/88 (1.14%) 
Otitis Media * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Papulopustular Rash * 1  0/127 (0.00%)  12/127 (9.45%)  1/88 (1.14%) 
Nail Infection * 1  1/127 (0.79%)  4/127 (3.15%)  0/88 (0.00%) 
Mucosal Infection * 1  1/127 (0.79%)  2/127 (1.57%)  1/88 (1.14%) 
Lung Infection * 1  2/127 (1.57%)  3/127 (2.36%)  9/88 (10.23%) 
Laryngitis * 1  0/127 (0.00%)  4/127 (3.15%)  0/88 (0.00%) 
Kidney Infection * 1  2/127 (1.57%)  3/127 (2.36%)  1/88 (1.14%) 
Paronychia * 1  0/127 (0.00%)  11/127 (8.66%)  9/88 (10.23%) 
Eye Infection * 1  1/127 (0.79%)  4/127 (3.15%)  1/88 (1.14%) 
Device Related Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Small Intestine Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Gum Infection * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Vaginal Infection * 1  2/127 (1.57%)  8/127 (6.30%)  2/88 (2.27%) 
Urinary Tract Infection * 1  18/127 (14.17%)  29/127 (22.83%)  14/88 (15.91%) 
Bronchial Infection * 1  1/127 (0.79%)  2/127 (1.57%)  1/88 (1.14%) 
Enterocolitis Infectious * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Lip Infection * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Anorectal Infection * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Bladder infection * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Injury, poisoning and procedural complications       
Vascular Access Complication * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Urostomy Obstruction * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Seroma * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Postoperative Hemorrhage * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Intestinal Stoma Site Bleeding * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Intestinal Stoma Obstruction * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Fracture * 1  1/127 (0.79%)  0/127 (0.00%)  2/88 (2.27%) 
Fall * 1  2/127 (1.57%)  3/127 (2.36%)  2/88 (2.27%) 
Wound Complication * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Dermatitis Radiation * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Burn * 1  0/127 (0.00%)  7/127 (5.51%)  0/88 (0.00%) 
Intestinal Stoma Leak * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Bruising * 1  3/127 (2.36%)  6/127 (4.72%)  0/88 (0.00%) 
Prolapse of intestinal stoma * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Ankle fracture * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Investigations       
Weight Loss * 1  5/127 (3.94%)  8/127 (6.30%)  9/88 (10.23%) 
Weight Gain * 1  2/127 (1.57%)  8/127 (6.30%)  2/88 (2.27%) 
Platelet Count Decreased * 1  13/127 (10.24%)  22/127 (17.32%)  8/88 (9.09%) 
Lymphocyte Count Increased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Lymphocyte Count Decreased * 1  6/127 (4.72%)  4/127 (3.15%)  2/88 (2.27%) 
Lipase Increased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Inr Increased * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Ggt Increased * 1  1/127 (0.79%)  1/127 (0.79%)  2/88 (2.27%) 
Electrocardiogram Qt Corrected Interval Prolonged * 1  0/127 (0.00%)  2/127 (1.57%)  2/88 (2.27%) 
Ejection Fraction Decreased * 1  1/127 (0.79%)  10/127 (7.87%)  7/88 (7.95%) 
Creatinine Increased * 1  10/127 (7.87%)  25/127 (19.69%)  15/88 (17.05%) 
Cholesterol High * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Neutrophil Count Decreased * 1  19/127 (14.96%)  21/127 (16.54%)  12/88 (13.64%) 
Cardiac Troponin I Increased * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Cpk Increased * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Cd4 Lymphocytes Decreased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Blood Bilirubin Increased * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
White Blood Cell Decreased * 1  21/127 (16.54%)  28/127 (22.05%)  17/88 (19.32%) 
Aspartate Aminotransferase Increased * 1  15/127 (11.81%)  47/127 (37.01%)  27/88 (30.68%) 
Alkaline Phosphatase Increased * 1  11/127 (8.66%)  31/127 (24.41%)  15/88 (17.05%) 
Alanine Aminotransferase Increased * 1  13/127 (10.24%)  27/127 (21.26%)  15/88 (17.05%) 
Activated Partial Thromboplastin Time Prolonged * 1  0/127 (0.00%)  4/127 (3.15%)  1/88 (1.14%) 
Metabolism and nutrition disorders       
Obesity * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hypophosphatemia * 1  4/127 (3.15%)  9/127 (7.09%)  4/88 (4.55%) 
Hyponatremia * 1  11/127 (8.66%)  16/127 (12.60%)  9/88 (10.23%) 
Hypomagnesemia * 1  29/127 (22.83%)  41/127 (32.28%)  28/88 (31.82%) 
Hypokalemia * 1  16/127 (12.60%)  27/127 (21.26%)  11/88 (12.50%) 
Hypoglycemia * 1  4/127 (3.15%)  5/127 (3.94%)  2/88 (2.27%) 
Hypocalcemia * 1  10/127 (7.87%)  25/127 (19.69%)  15/88 (17.05%) 
Hypoalbuminemia * 1  16/127 (12.60%)  42/127 (33.07%)  24/88 (27.27%) 
Hypertriglyceridemia * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hypernatremia * 1  2/127 (1.57%)  8/127 (6.30%)  3/88 (3.41%) 
Hypermagnesemia * 1  3/127 (2.36%)  1/127 (0.79%)  1/88 (1.14%) 
Hyperkalemia * 1  5/127 (3.94%)  5/127 (3.94%)  5/88 (5.68%) 
Hyperglycemia * 1  25/127 (19.69%)  32/127 (25.20%)  16/88 (18.18%) 
Hypercalcemia * 1  4/127 (3.15%)  4/127 (3.15%)  1/88 (1.14%) 
Dehydration * 1  10/127 (7.87%)  11/127 (8.66%)  7/88 (7.95%) 
Anorexia * 1  24/127 (18.90%)  33/127 (25.98%)  35/88 (39.77%) 
Musculoskeletal and connective tissue disorders       
Pain In Extremity * 1  9/127 (7.09%)  9/127 (7.09%)  6/88 (6.82%) 
Neck Pain * 1  3/127 (2.36%)  5/127 (3.94%)  3/88 (3.41%) 
Myalgia * 1  15/127 (11.81%)  16/127 (12.60%)  10/88 (11.36%) 
Muscle Weakness Trunk * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Muscle Weakness Lower Limb * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Joint Range Of Motion Decreased * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Joint Effusion * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Generalized Muscle Weakness * 1  2/127 (1.57%)  10/127 (7.87%)  6/88 (6.82%) 
Flank Pain * 1  2/127 (1.57%)  3/127 (2.36%)  1/88 (1.14%) 
Chest Wall Pain * 1  3/127 (2.36%)  3/127 (2.36%)  3/88 (3.41%) 
Bone Pain * 1  4/127 (3.15%)  0/127 (0.00%)  1/88 (1.14%) 
Back Pain * 1  24/127 (18.90%)  24/127 (18.90%)  20/88 (22.73%) 
Arthritis * 1  3/127 (2.36%)  6/127 (4.72%)  2/88 (2.27%) 
Arthralgia * 1  21/127 (16.54%)  11/127 (8.66%)  15/88 (17.05%) 
Musculoskeletal And Connective Tissue Disorder - O * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Muscle weakness upper limb * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor Pain * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Nervous system disorders       
Tremor * 1  0/127 (0.00%)  4/127 (3.15%)  1/88 (1.14%) 
Stroke * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Presyncope * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Peripheral Sensory Neuropathy * 1  28/127 (22.05%)  36/127 (28.35%)  17/88 (19.32%) 
Peripheral Motor Neuropathy * 1  2/127 (1.57%)  5/127 (3.94%)  0/88 (0.00%) 
Paresthesia * 1  6/127 (4.72%)  3/127 (2.36%)  5/88 (5.68%) 
Memory Impairment * 1  6/127 (4.72%)  6/127 (4.72%)  4/88 (4.55%) 
Lethargy * 1  1/127 (0.79%)  1/127 (0.79%)  2/88 (2.27%) 
Headache * 1  24/127 (18.90%)  28/127 (22.05%)  20/88 (22.73%) 
Dysphasia * 1  3/127 (2.36%)  0/127 (0.00%)  0/88 (0.00%) 
Dysgeusia * 1  4/127 (3.15%)  11/127 (8.66%)  8/88 (9.09%) 
Sinus Pain * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Dysarthria * 1  0/127 (0.00%)  3/127 (2.36%)  0/88 (0.00%) 
Syncope * 1  0/127 (0.00%)  2/127 (1.57%)  1/88 (1.14%) 
Dizziness * 1  7/127 (5.51%)  22/127 (17.32%)  11/88 (12.50%) 
Concentration Impairment * 1  1/127 (0.79%)  1/127 (0.79%)  2/88 (2.27%) 
Cognitive Disturbance * 1  1/127 (0.79%)  2/127 (1.57%)  1/88 (1.14%) 
Psychiatric disorders       
Personality Change * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Restlessness * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Libido Decreased * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Insomnia * 1  24/127 (18.90%)  16/127 (12.60%)  17/88 (19.32%) 
Depression * 1  11/127 (8.66%)  26/127 (20.47%)  10/88 (11.36%) 
Confusion * 1  1/127 (0.79%)  3/127 (2.36%)  3/88 (3.41%) 
Anxiety * 1  12/127 (9.45%)  15/127 (11.81%)  11/88 (12.50%) 
Agitation * 1  1/127 (0.79%)  3/127 (2.36%)  0/88 (0.00%) 
Delirium * 1  0/127 (0.00%)  0/127 (0.00%)  2/88 (2.27%) 
Renal and urinary disorders       
Urine Discoloration * 1  1/127 (0.79%)  1/127 (0.79%)  0/88 (0.00%) 
Urinary Urgency * 1  2/127 (1.57%)  8/127 (6.30%)  4/88 (4.55%) 
Urinary Tract Obstruction * 1  2/127 (1.57%)  5/127 (3.94%)  3/88 (3.41%) 
Urinary Retention * 1  2/127 (1.57%)  4/127 (3.15%)  5/88 (5.68%) 
Urinary Incontinence * 1  5/127 (3.94%)  10/127 (7.87%)  5/88 (5.68%) 
Urinary Tract Pain * 1  6/127 (4.72%)  10/127 (7.87%)  2/88 (2.27%) 
Urinary Frequency * 1  9/127 (7.09%)  10/127 (7.87%)  9/88 (10.23%) 
Proteinuria * 1  2/127 (1.57%)  7/127 (5.51%)  3/88 (3.41%) 
Hematuria * 1  3/127 (2.36%)  20/127 (15.75%)  4/88 (4.55%) 
Cystitis Noninfective * 1  2/127 (1.57%)  1/127 (0.79%)  1/88 (1.14%) 
Chronic Kidney Disease * 1  3/127 (2.36%)  1/127 (0.79%)  2/88 (2.27%) 
Bladder Spasm * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Acute Kidney Injury * 1  3/127 (2.36%)  0/127 (0.00%)  4/88 (4.55%) 
Reproductive system and breast disorders       
Vaginal Pain * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Vaginal Hemorrhage * 1  8/127 (6.30%)  3/127 (2.36%)  6/88 (6.82%) 
Vaginal Fistula * 1  1/127 (0.79%)  0/127 (0.00%)  1/88 (1.14%) 
Vaginal Dryness * 1  4/127 (3.15%)  5/127 (3.94%)  2/88 (2.27%) 
Uterine Pain * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Pelvic Pain * 1  5/127 (3.94%)  5/127 (3.94%)  2/88 (2.27%) 
Menorrhagia * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Vaginal Discharge * 1  8/127 (6.30%)  3/127 (2.36%)  6/88 (6.82%) 
Vaginal Inflammation * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Dyspareunia * 1  3/127 (2.36%)  2/127 (1.57%)  2/88 (2.27%) 
Breast Pain * 1  2/127 (1.57%)  0/127 (0.00%)  0/88 (0.00%) 
Genital Edema * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Respiratory, thoracic and mediastinal disorders       
Voice Alteration * 1  0/127 (0.00%)  1/127 (0.79%)  2/88 (2.27%) 
Sore Throat * 1  3/127 (2.36%)  6/127 (4.72%)  8/88 (9.09%) 
Sneezing * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Sinus Disorder * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Respiratory Failure * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Pulmonary Hypertension * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Postnasal Drip * 1  0/127 (0.00%)  2/127 (1.57%)  4/88 (4.55%) 
Pneumothorax * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Pneumonitis * 1  0/127 (0.00%)  3/127 (2.36%)  3/88 (3.41%) 
Pleural Effusion * 1  7/127 (5.51%)  6/127 (4.72%)  6/88 (6.82%) 
Pharyngeal Mucositis * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Nasal Congestion * 1  5/127 (3.94%)  7/127 (5.51%)  6/88 (6.82%) 
Pleuritic Pain * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Productive Cough * 1  2/127 (1.57%)  2/127 (1.57%)  6/88 (6.82%) 
Laryngeal Inflammation * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Hoarseness * 1  0/127 (0.00%)  2/127 (1.57%)  6/88 (6.82%) 
Sleep Apnea * 1  2/127 (1.57%)  1/127 (0.79%)  3/88 (3.41%) 
Hiccups * 1  1/127 (0.79%)  1/127 (0.79%)  1/88 (1.14%) 
Epistaxis * 1  1/127 (0.79%)  15/127 (11.81%)  12/88 (13.64%) 
Dyspnea * 1  27/127 (21.26%)  44/127 (34.65%)  26/88 (29.55%) 
Cough * 1  21/127 (16.54%)  30/127 (23.62%)  19/88 (21.59%) 
Chylothorax * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Bronchospasm * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Bronchopulmonary Hemorrhage * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Allergic Rhinitis * 1  6/127 (4.72%)  7/127 (5.51%)  6/88 (6.82%) 
Wheezing * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Hypoxia * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Respiratory, Thoracic and Mediastinal Disorders * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
Skin and subcutaneous tissue disorders       
Urticaria * 1  0/127 (0.00%)  6/127 (4.72%)  2/88 (2.27%) 
Skin Ulceration * 1  2/127 (1.57%)  8/127 (6.30%)  5/88 (5.68%) 
Skin Induration * 1  0/127 (0.00%)  1/127 (0.79%)  0/88 (0.00%) 
Skin Hyperpigmentation * 1  4/127 (3.15%)  3/127 (2.36%)  4/88 (4.55%) 
Scalp Pain * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Rash Acneiform * 1  13/127 (10.24%)  80/127 (62.99%)  50/88 (56.82%) 
Purpura * 1  1/127 (0.79%)  0/127 (0.00%)  0/88 (0.00%) 
Pruritus * 1  7/127 (5.51%)  25/127 (19.69%)  18/88 (20.45%) 
Photosensitivity * 1  0/127 (0.00%)  4/127 (3.15%)  0/88 (0.00%) 
Periorbital Edema * 1  0/127 (0.00%)  6/127 (4.72%)  4/88 (4.55%) 
Palmar-Plantar Erythrodysesthesia Syndrome * 1  21/127 (16.54%)  8/127 (6.30%)  10/88 (11.36%) 
Pain Of Skin * 1  2/127 (1.57%)  4/127 (3.15%)  3/88 (3.41%) 
Rash Maculo-Papular * 1  28/127 (22.05%)  54/127 (42.52%)  30/88 (34.09%) 
Nail Ridging * 1  0/127 (0.00%)  1/127 (0.79%)  1/88 (1.14%) 
Nail Loss * 1  1/127 (0.79%)  2/127 (1.57%)  4/88 (4.55%) 
Nail Discoloration * 1  3/127 (2.36%)  4/127 (3.15%)  1/88 (1.14%) 
Hypertrichosis * 1  0/127 (0.00%)  3/127 (2.36%)  0/88 (0.00%) 
Hyperhidrosis * 1  1/127 (0.79%)  1/127 (0.79%)  3/88 (3.41%) 
Hirsutism * 1  1/127 (0.79%)  4/127 (3.15%)  3/88 (3.41%) 
Erythema Multiforme * 1  1/127 (0.79%)  2/127 (1.57%)  0/88 (0.00%) 
Dry Skin * 1  17/127 (13.39%)  56/127 (44.09%)  40/88 (45.45%) 
Bullous Dermatitis * 1  0/127 (0.00%)  2/127 (1.57%)  0/88 (0.00%) 
Alopecia * 1  16/127 (12.60%)  28/127 (22.05%)  21/88 (23.86%) 
Vascular disorders       
Thromboembolic Event * 1  6/127 (4.72%)  11/127 (8.66%)  4/88 (4.55%) 
Lymphedema * 1  3/127 (2.36%)  5/127 (3.94%)  1/88 (1.14%) 
Hypotension * 1  2/127 (1.57%)  5/127 (3.94%)  3/88 (3.41%) 
Hypertension * 1  27/127 (21.26%)  49/127 (38.58%)  30/88 (34.09%) 
Hot Flashes * 1  35/127 (27.56%)  14/127 (11.02%)  13/88 (14.77%) 
Flushing * 1  3/127 (2.36%)  3/127 (2.36%)  0/88 (0.00%) 
Superior Vena Cava Syndrome * 1  0/127 (0.00%)  0/127 (0.00%)  1/88 (1.14%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Linda Gedeon for Austin Miller, PhD
Organization: NRG Oncology
Phone: 716-845-1169
EMail: linda.gedeon@roswellpark.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02101788    
Other Study ID Numbers: NCI-2014-00629
NCI-2014-00629 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
GOG-0281 ( Other Identifier: NRG Oncology )
GOG-0281 ( Other Identifier: CTEP )
P50CA083639 ( U.S. NIH Grant/Contract )
U10CA180868 ( U.S. NIH Grant/Contract )
First Submitted: March 28, 2014
First Posted: April 2, 2014
Results First Submitted: May 11, 2020
Results First Posted: September 29, 2020
Last Update Posted: May 3, 2021