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

Phase 2

Active, not recruiting

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

Registration Number: NCT01142388

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 94

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (paclitaxel)	Laboratory Biomarker Analysis	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
Arm I (paclitaxel)	Pharmacological Study	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
Arm II (cixutumumab, paclitaxel)	Cixutumumab	Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
Arm II (cixutumumab, paclitaxel)	Laboratory Biomarker Analysis	Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
Arm II (cixutumumab, paclitaxel)	Paclitaxel	Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
Arm II (cixutumumab, paclitaxel)	Pharmacological Study	Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
Arm I (paclitaxel)	Paclitaxel	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	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	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.

Trial Locations

Locations (232): Beacon Kalamazoo
🇺🇸
Kalamazoo, Michigan, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Boulder Community Foothills Hospital
🇺🇸
Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
AdventHealth Porter
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Saint Joseph Hospital - Cancer Centers of Colorado
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
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Beacon Kalamazoo
🇺🇸Kalamazoo, Michigan, United States