Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

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ClinicalTrials.gov Identifier: NCT01142388

Recruitment Status : Active, not recruiting

First Posted : June 11, 2010

Results First Posted : June 3, 2015

Last Update Posted : November 17, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Metastatic Esophageal Adenocarcinoma Metastatic Esophageal Squamous Cell Carcinoma Metastatic Gastroesophageal Junction Adenocarcinoma Recurrent Esophageal Adenocarcinoma Recurrent Esophageal Carcinoma Recurrent Esophageal Squamous Cell Carcinoma Recurrent Gastroesophageal Junction Adenocarcinoma Stage IV Esophageal Cancer AJCC v7
Interventions	Biological: Cixutumumab Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Pharmacological Study
Enrollment	94

Participant Flow

Recruitment Details	This study was activated on September 21, 2010 and closed to accrual on October 15, 2012 with total accrual of 94 patients from 27 ECOG-ACRIN affiliated institutions.
Pre-assignment Details


Arm/Group Title	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...
Arm/Group Description	Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Period Title: Overall Study
Started	47	47
Eligible	43	44
Treated	40	44
Completed	0 ^[1]	0
Not Completed	47	47
Reason Not Completed
Lack of Efficacy	21	31
Adverse Event	9	5
Death	3	2
Withdrawal by Subject	5	3
Alternative therapy	1	0
Other complications	0	2
Other	1	1
Never started therapy	7	3
[1] Treatment continued until disease progression or intolerable toxicity.

Baseline Characteristics

Arm/Group Title		Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)	Total
Arm/Group Description		Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...	Total of all reporting groups
Arm/Group Description		Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV	Total of all reporting groups
Overall Number of Baseline Participants		43	44	87
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Per protocol, the primary population for all efficacy endpoints is all eligible patients
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	43 participants	44 participants	87 participants
		63 (40 to 89)	62 (40 to 82)	62 (40 to 89)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	43 participants	44 participants	87 participants
	Female	8 18.6%	11 25.0%	19 21.8%
	Male	35 81.4%	33 75.0%	68 78.2%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	43 participants	44 participants	87 participants
United States		43	44	87

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival
Description	Progression-free survival (PFS) is defined as the time from randomizat...
Description	Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was counted as an event, or in the case of death within 4 months of randomization in the absence of disease evaluation before that time. PFS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.
Time Frame	assessed every 3 months for 2 years after registration

Outcome Measure Data

Analysis Population Description

Eligible patients.


Arm/Group Title	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
Arm/Group Description:	Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...
Arm/Group Description:	Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Number of Participants Analyzed	43	44
Median (90% Confidence Interval) Unit of Measure: months
	2.6 (1.8 to 4.1)	2.3 (2.0 to 3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Paclitaxel), Arm II (Cixutumumab, Paclitaxel)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.85
	Comments	[Not Specified]
	Method	Log Rank
	Comments	one-sided stratified log rank test, stratifying on: 1) gastroesophageal junction vs. esophagus, 2) squamous cell carcinoma vs. adenocarcinoma.

2.Secondary Outcome


Title	Overall Survival
Description	Overall survival (OS) is defined as the time from randomization until ...
Description	Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.
Time Frame	assessed every 3 months for 2 years after registration

Outcome Measure Data

Analysis Population Description

Eligible patients


Arm/Group Title	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
Arm/Group Description:	Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...
Arm/Group Description:	Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Number of Participants Analyzed	43	44
Median (90% Confidence Interval) Unit of Measure: months
	6.5 (4.6 to 9.5)	6.4 (4.9 to 8.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Paclitaxel), Arm II (Cixutumumab, Paclitaxel)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.50
	Comments	[Not Specified]
	Method	Log Rank
	Comments	one-sided stratified log rank test, stratifying on 1) gastroesophageal junction vs. esophagus, 2) squamous cell carcinoma vs. adenocarcinoma.

3.Secondary Outcome


Title	Objective Response Rate
Description	Objective response rate is defined as number of patients with complete...
Description	Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Time Frame	assessed every 8 weeks while on treatment and every 3 months after treatment for 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients


Arm/Group Title	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
Arm/Group Description:	Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...
Arm/Group Description:	Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Number of Participants Analyzed	43	44
Measure Type: Number Number (90% Confidence Interval) Unit of Measure: percentage of participants
	12 (5 to 23)	14 (6 to 25)

Adverse Events

Time Frame	Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description	Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.

Arm/Group Title	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
Arm/Group Description	Patients receive paclitaxel IV over...	Patients receive cixutumumab IV ove...
Arm/Group Description	Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
All-Cause Mortality
	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	21/40 (52.50%)	23/44 (52.27%)
Blood and lymphatic system disorders
Anemia ^† 1	4/40 (10.00%)	4/44 (9.09%)
Leukocytosis ^† 1	1/40 (2.50%)	1/44 (2.27%)
Cardiac disorders
Atrial fibrillation ^† 1	0/40 (0.00%)	1/44 (2.27%)
Left ventricular systolic dysfunction ^† 1	0/40 (0.00%)	1/44 (2.27%)
Gastrointestinal disorders
Abdominal pain ^† 1	1/40 (2.50%)	0/44 (0.00%)
Gastric perforation ^† 1	1/40 (2.50%)	0/44 (0.00%)
Mucositis oral ^† 1	0/40 (0.00%)	2/44 (4.55%)
Nausea ^† 1	1/40 (2.50%)	1/44 (2.27%)
Upper gastrointestinal hemorrhage ^† 1	1/40 (2.50%)	0/44 (0.00%)
Vomiting ^† 1	0/40 (0.00%)	2/44 (4.55%)
General disorders
Death NOS ^† 1	1/40 (2.50%)	0/44 (0.00%)
Fatigue ^† 1	4/40 (10.00%)	1/44 (2.27%)
Infusion related reaction ^† 1	1/40 (2.50%)	0/44 (0.00%)
Infections and infestations
Sepsis ^† 1	1/40 (2.50%)	0/44 (0.00%)
Investigations
Alkaline phosphatase increased ^† 1	1/40 (2.50%)	0/44 (0.00%)
Aspartate aminotransferase increased ^† 1	1/40 (2.50%)	0/44 (0.00%)
Blood bilirubin increased ^† 1	1/40 (2.50%)	0/44 (0.00%)
Lymphocyte count decreased ^† 1	8/40 (20.00%)	8/44 (18.18%)
Neutrophil count decreased ^† 1	3/40 (7.50%)	8/44 (18.18%)
Platelet count decreased ^† 1	0/40 (0.00%)	1/44 (2.27%)
Weight loss ^† 1	0/40 (0.00%)	1/44 (2.27%)
White blood cell decreased ^† 1	2/40 (5.00%)	6/44 (13.64%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/40 (0.00%)	1/44 (2.27%)
Glucose intolerance ^† 1	0/40 (0.00%)	1/44 (2.27%)
Hyperglycemia ^† 1	2/40 (5.00%)	5/44 (11.36%)
Hypokalemia ^† 1	1/40 (2.50%)	0/44 (0.00%)
Hyponatremia ^† 1	0/40 (0.00%)	1/44 (2.27%)
Hypophosphatemia ^† 1	2/40 (5.00%)	1/44 (2.27%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness ^† 1	0/40 (0.00%)	2/44 (4.55%)
Myalgia ^† 1	1/40 (2.50%)	0/44 (0.00%)
Neck pain ^† 1	1/40 (2.50%)	0/44 (0.00%)
Nervous system disorders
Peripheral motor neuropathy ^† 1	0/40 (0.00%)	1/44 (2.27%)
Peripheral sensory neuropathy ^† 1	1/40 (2.50%)	1/44 (2.27%)
Syncope ^† 1	1/40 (2.50%)	0/44 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	0/40 (0.00%)	1/44 (2.27%)
Pneumonitis ^† 1	1/40 (2.50%)	0/44 (0.00%)
Respiratory failure ^† 1	0/40 (0.00%)	1/44 (2.27%)
Skin and subcutaneous tissue disorders
Rash maculo-papular ^† 1	1/40 (2.50%)	0/44 (0.00%)
Vascular disorders
Hypertension ^† 1	0/40 (0.00%)	1/44 (2.27%)
Hypotension ^† 1	0/40 (0.00%)	1/44 (2.27%)
Vascular disorders - Other, specify ^† 1	0/40 (0.00%)	1/44 (2.27%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE 4.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (Paclitaxel)	Arm II (Cixutumumab, Paclitaxel)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	39/40 (97.50%)	43/44 (97.73%)
Blood and lymphatic system disorders
Anemia ^† 1	29/40 (72.50%)	29/44 (65.91%)
Eye disorders
Flashing lights ^† 1	0/40 (0.00%)	7/44 (15.91%)
Floaters ^† 1	0/40 (0.00%)	3/44 (6.82%)
Gastrointestinal disorders
Constipation ^† 1	4/40 (10.00%)	2/44 (4.55%)
Diarrhea ^† 1	8/40 (20.00%)	10/44 (22.73%)
Mucositis oral ^† 1	2/40 (5.00%)	5/44 (11.36%)
Nausea ^† 1	8/40 (20.00%)	14/44 (31.82%)
Vomiting ^† 1	6/40 (15.00%)	9/44 (20.45%)
General disorders
Edema limbs ^† 1	4/40 (10.00%)	1/44 (2.27%)
Fatigue ^† 1	27/40 (67.50%)	27/44 (61.36%)
Investigations
Alanine aminotransferase increased ^† 1	5/40 (12.50%)	4/44 (9.09%)
Alkaline phosphatase increased ^† 1	5/40 (12.50%)	10/44 (22.73%)
Aspartate aminotransferase increased ^† 1	5/40 (12.50%)	8/44 (18.18%)
Creatinine increased ^† 1	0/40 (0.00%)	4/44 (9.09%)
Lymphocyte count decreased ^† 1	17/40 (42.50%)	15/44 (34.09%)
Neutrophil count decreased ^† 1	10/40 (25.00%)	14/44 (31.82%)
Platelet count decreased ^† 1	6/40 (15.00%)	10/44 (22.73%)
Weight loss ^† 1	8/40 (20.00%)	8/44 (18.18%)
White blood cell decreased ^† 1	13/40 (32.50%)	18/44 (40.91%)
Metabolism and nutrition disorders
Anorexia ^† 1	7/40 (17.50%)	12/44 (27.27%)
Glucose intolerance ^† 1	3/40 (7.50%)	5/44 (11.36%)
Hyperglycemia ^† 1	9/40 (22.50%)	17/44 (38.64%)
Hypoalbuminemia ^† 1	3/40 (7.50%)	4/44 (9.09%)
Hypocalcemia ^† 1	0/40 (0.00%)	5/44 (11.36%)
Hypokalemia ^† 1	3/40 (7.50%)	3/44 (6.82%)
Hypomagnesemia ^† 1	5/40 (12.50%)	6/44 (13.64%)
Hyponatremia ^† 1	3/40 (7.50%)	8/44 (18.18%)
Hypophosphatemia ^† 1	3/40 (7.50%)	2/44 (4.55%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/40 (2.50%)	3/44 (6.82%)
Myalgia ^† 1	1/40 (2.50%)	5/44 (11.36%)
Pain in extremity ^† 1	0/40 (0.00%)	4/44 (9.09%)
Nervous system disorders
Dizziness ^† 1	2/40 (5.00%)	5/44 (11.36%)
Dysgeusia ^† 1	1/40 (2.50%)	5/44 (11.36%)
Headache ^† 1	1/40 (2.50%)	4/44 (9.09%)
Paresthesia ^† 1	3/40 (7.50%)	0/44 (0.00%)
Peripheral sensory neuropathy ^† 1	14/40 (35.00%)	16/44 (36.36%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	13/40 (32.50%)	12/44 (27.27%)
Pruritus ^† 1	3/40 (7.50%)	5/44 (11.36%)
Rash acneiform ^† 1	1/40 (2.50%)	5/44 (11.36%)
Rash maculo-papular ^† 1	2/40 (5.00%)	8/44 (18.18%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE 4.0

Limitations and Caveats

[Not Specified]

More Information

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:	Study Statistician
Organization:	ECOG-ACRIN Statistical Office
Phone:	617-632-3012

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01142388
Other Study ID Numbers:	NCI-2011-02045 NCI-2011-02045 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ECOG-E2208 CDR0000674327 E2208 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) E2208 ( Other Identifier: CTEP ) U10CA180820 ( U.S. NIH Grant/Contract ) U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted:	June 10, 2010
First Posted:	June 11, 2010
Results First Submitted:	May 13, 2015
Results First Posted:	June 3, 2015
Last Update Posted:	November 17, 2022

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