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

• 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
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: June 10, 2010
• First Posted Date: June 11, 2010
• Results First Submitted Date: May 13, 2015
• Results First Posted Date: June 3, 2015
• Last Update Posted Date: November 17, 2022
• Actual Study Start Date: September 21, 2010
• Actual Primary Completion Date: July 15, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2015)

Progression-free Survival [ Time Frame: assessed every 3 months for 2 years after registration ]

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.

• Original Primary Outcome Measures (submitted: June 10, 2010): Progression-free survival

Current Secondary Outcome Measures (submitted: June 2, 2015)

• Overall Survival [ Time Frame: assessed every 3 months for 2 years after registration ]
  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.
• Objective Response Rate [ Time Frame: assessed every 8 weeks while on treatment and every 3 months after treatment for 2 years ]
  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.

Original Secondary Outcome Measures (submitted: June 10, 2010)

• Overall survival
• Response rate

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer
• Official Title: Randomized Phase II Study of Paclitaxel With or Without the Anti-IGF-IR mAb Cixutumumab (IMC-A12) as Second Line Treatment for Patients With Metastatic Esophageal or GE Junction Cancer
• Brief Summary: This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with esophageal cancer or gastroesophageal junction cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cixutumumab may kill cancer cells by blocking the action of a protein needed for cancer cell growth. Giving paclitaxel with or without cixutumumab may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone as second-line therapy in patients with metastatic esophagus or gastroesophageal (GE) junction cancer.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

II. To evaluate the response rate of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

III. To evaluate the toxicity of cixutumumab (IMC-A12) plus paclitaxel versus paclitaxel alone in this patient population.

IV. Exploratory analyses will assess potentially relevant cixutumumab (IMC-A12) pharmacodynamic biomarkers obtained from serum samples, including but not limited to, insulin-like growth factor (IGF)-I, IGF-II, insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-3.

OUTLINE: Patients are equally randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle.

ARM II: 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.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Biological: Cixutumumab
  Given IV
  Other Names:

  • Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12
  • IMC-A12
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Drug: Paclitaxel
  Given IV
  Other Names:

  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
• Other: Pharmacological Study
  Correlative studies

Study Arms

• Experimental: Arm I (paclitaxel)
  Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
  Interventions:

  • Other: Laboratory Biomarker Analysis
  • Drug: Paclitaxel
  • Other: Pharmacological Study
• Experimental: Arm II (cixutumumab, paclitaxel)
  Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
  Interventions:

  • Biological: Cixutumumab
  • Other: Laboratory Biomarker Analysis
  • Drug: Paclitaxel
  • Other: Pharmacological Study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 28, 2014): 94
• Original Estimated Enrollment (submitted: June 10, 2010): 90
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 15, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Life expectancy >= 12 weeks
• Women must not be pregnant or breast-feeding due to potential harm to fetus from cixutumumab (IMC-A12) and paclitaxel; all females of childbearing potential must have a blood test or urine study within 48 hours prior to registration to rule out pregnancy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method or birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of cixutumumab (IMC-A12); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Patients must have measurable disease

• Patients must have metastatic disease of the esophagus or gastroesophageal junction

  • Histologic, cytologic or radiologic documentation of metastatic squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction; radiologic, endoscopic, histologic or cytologic evidence of locally recurrent or locally residual (post-resection) disease is also permitted
  • For the purposes of this study, undifferentiated adenocarcinomas and adenosquamous tumors will be considered as adenocarcinomas; in addition, tumors involving the gastroesophageal junction will be defined by the Siewert classification

• Patients with gastroesophageal junction tumors who are eligible:

  • Adenocarcinoma of the esophageal junction (AEG) Type I: adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus, i.e., Barrett's esophagus, and may infiltrate the esophagogastric junction from above
  • AEG Type II: true carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the esophagogastric junction

• Patients with gastroesophageal junction tumors who are NOT eligible:

  • AEG Type III: subcardial gastric carcinoma which infiltrates the esophagogastric junction and distal esophagus from below

• Patients must have received and progressed on one and only one line of prior systemic therapy for esophagus or esophagogastric cancer; this could have included one regimen for metastatic disease, or one regimen with radiotherapy for initially locally advanced disease; prior radiation therapy is permitted

  • If patients progress or recur within 6 months of neoadjuvant/adjuvant therapy, this will be considered one line of therapy; for patients progressing or recurring more than 6 months after neoadjuvant/adjuvant therapy, they will need to receive one line of therapy for recurrent disease to be eligible
  • If patients receive one regimen in which a chemotherapy agent is dropped for toxicity without progression, this treatment will be considered one line of therapy; however, substitution or addition of a new agent will be considered a second line of therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Leukocytes > 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mcL
• Total bilirubin =< institutional upper limit of normal (ULN)
• Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
• Creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
• Patients must have fasting serum glucose =< 160 mg/dL (8.8 mmol/L) or =< ULN, and hemoglobin A1C =< 7% (0.07 International System of Units [SI units]) within 14 days of registration; if baseline nonfasting glucose =< 160 mg/dL (8.8 mmol/L), fasting glucose measurement is not required
• Registration no fewer than 28 days from last chemotherapy
• A "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse

Exclusion Criteria:

• Patients have received prior taxane or anti-insulin growth factor receptor (IGFR) therapy

• Patients must not have any of the following conditions:

  • Poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose =< 160 mg/dL [8.8 mmol/L] or below the ULN and hemoglobin A1C =< 7% [0.07 SI units]) and that they are on a stable dietary or therapeutic regimen for this condition
  • Recent major surgery, hormonal therapy (other than replacement) or chemotherapy, within 4 weeks prior to entering the study or those who have not recovered from adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cixutumumab (IMC-A12)
  • Psychiatric illness that would prevent the patient from giving informed consent
• Medical conditions such as active/uncontrolled infection (including HIV) or cardiac disease that would make this protocol unreasonably hazardous for the patient in the opinion of the treating physician; cardiac disease may include uncontrolled high blood pressure, unstable angina, or serious uncontrolled cardiac arrhythmia

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Robert L. Comis, ECOG Group Chair's Office
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Eastern Cooperative Oncology Group
• Collaborators: Not Provided

Investigators

• Principal Investigator: Steven J Cohen; ECOG-ACRIN Cancer Research Group

• PRS Account: National Cancer Institute (NCI)
• Verification Date: November 2022