Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer
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
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Adenocarcinoma; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Recurrence
Intervention: Cixutumumab; Laboratory Biomarker Analysis; Paclitaxel; Pharmacological Study
Intervention description: Given IV; Correlative studies; Given IV; Correlative studies
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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