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 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, IGF-I, IGF-II, IGFBP-2, and IGFBP-3.
OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (gastroesophageal junction vs esophageal cancer) and cell type (squamous cell carcinoma vs adenocarcinoma). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel intravenously (IV) over I hour on days 1, 8, and 15.
ARM II: Patients receive cixutumumab IV over 1 hour on days 1 and 15, 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 therapy, patients are followed up every 3 months for 2 years.
Inclusion Criteria:
- Histologically, cytologically, or radiologically confirmed metastatic esophageal or gastroesophageal junction meeting 1 of the following criteria:
- Squamous cell carcinoma
- Adenocarcinoma
- Undifferentiated adenocarcinomas and adenosquamous tumors will be considered as adenocarcinomas
- Patients with adenocarcinoma of the gastroesophageal or esophagogastric (AEG) junction tumors meeting the following:
- AEG type I: adenocarcinoma of the distal esophagus that usually arises from an area with specialized intestinal metaplasia of the esophagus (i.e., Barrett 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
- No AEG type III: subcardial gastric carcinoma that infiltrates the esophagogastric junction and distal esophagus from below
- Evidence of local recurrence or local residual (post-resection) disease by radiology, endoscopy, histology, or cytology allowed
- Measurable disease
- Must have received and progressed on 1 line of prior systemic therapy for esophageal or esophagogastric cancer meeting ≥ 1 of the following criteria:
- May have included one regimen for metastatic disease, or one regimen with radiotherapy for initially locally advanced disease
- 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 1 line of therapy
- Substitution or addition of a new agent will be considered a second line of therapy
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- Leukocytes ≥ 3,000/mm^3
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Total bilirubin normal
- AST and/or ALT ≤ 3 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Fasting serum glucose ≤ 160 mg/dL and hemoglobin A_1C ≤ 7%
- Fasting glucose not required if non-fasting glucose ≤ 160 mg/dL
- History of diabetes mellitus allowed provided blood glucose is within normal range and patients are on a stable dietary or therapeutic regimen
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study therapy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cixutumumab
- No psychiatric illness that would prevent the patient from giving informed consent
- None of the following medical conditions that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
- Active and/or uncontrolled infection, including HIV positivity
- Cardiac disease including, but not limited to, any of the following:
- Uncontrolled high-blood pressure
- Unstable angina
- Serious uncontrolled cardiac arrhythmia
- No currently active second malignancy except nonmelanoma skin cancer or curatively treated malignancy with < 30% risk of relapse
- No prior treatment with other agents targeting the IGFR
- More than 4 weeks since prior major surgery, hormonal therapy (other than replacement), or chemotherapy and recovered
- No prior taxane or anti-IGFR therapy
Last updated: 03/18/2013
NCT ID: NCT01142388
IRB Number:10-007765
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