C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

NCT02344810 | Withdrawn Phase 1 DMC

• 3 other identifiers: EA2132NCI-2014-01315U10CA180820
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of c-Met inhibitor AMG 337 when given together with oxaliplatin, leucovorin calcium, and fluorouracil and to see how well they work in treating patients with stomach or esophageal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. C-Met inhibitor AMG 337 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as, oxaliplatin, leucovorin calcium, and fluorouracil, 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. Giving c-Met inhibitor AMG 337 with oxaliplatin, leucovorin calcium, and fluorouracil may kill more tumor cells.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of c-Met inhibitor AMG 337, defined as the highest dose level at which < 33% of 6 patients experience a dose limiting toxicity graded according to CTCAE v.4 (Phase I)

  28 days

• Progression-free survival (Phase II)

  The study will have 90% power to detect the above improvement in PFS using a one-sided 0.10 level log rank test.

  Up to 2 years

Secondary Outcomes (7)

• Overall survival (Phase II)

  Up to 2 years

• Response rate (Phase II)

  Up to 2 years

• Disease control rate (Phase II)

  Up to 2 years

• Incidence of toxicity graded according to CTCAE v.4 (Phase II)

  Up to 2 years

• Time to development of new metastasis (Phase II)

  Up to 2 years

Study Arms (2)

Arm A (AMG 337, mFOLFOX6)

EXPERIMENTAL

Patients receive c-Met inhibitor AMG 337 PO QD on days 1-28; and oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on days 1 and 15.

Drug: c-Met inhibitor AMG 337; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: pharmacological study; Other: laboratory biomarker analysis

Arm B (placebo, mFOLFOX6)

ACTIVE COMPARATOR

Patients receive placebo PO QD on days 1-28; and oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on days 1 and 15.

Other: placebo; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

c-Met inhibitor AMG 337 DRUG

Given PO

Also known as: AMG 337, AMG337

Arm A (AMG 337, mFOLFOX6)

placebo OTHER

Given PO

Also known as: PLCB

Arm B (placebo, mFOLFOX6)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Arm A (AMG 337, mFOLFOX6); Arm B (placebo, mFOLFOX6)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Arm A (AMG 337, mFOLFOX6); Arm B (placebo, mFOLFOX6)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Arm A (AMG 337, mFOLFOX6); Arm B (placebo, mFOLFOX6)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm A (AMG 337, mFOLFOX6); Arm B (placebo, mFOLFOX6)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (AMG 337, mFOLFOX6); Arm B (placebo, mFOLFOX6)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a life expectancy \>= 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 48 hours prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of AMG 337 plus mFOLFOX6 chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; should a man impregnate or suspect that he has impregnated a woman while participating in this study, he should inform his treating physician immediately
• Patients must NOT have a known immediate or delayed hypersensitivity reaction to drugs chemically related to fluorouracil, platins or their excipients nor have a known history of dihydropyrimidine dehydrogenase (DPD) deficiency
• Patients must be able to swallow tablets whole
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 X institutional upper limit of normal (ULN) or =\< 5 X ULN if the patient has liver metastases
• Creatinine =\< 1.5 X institutional ULN or creatinine clearance \>= 50 mL/min for patients with creatinine levels above institutional normal
• Patients must NOT be taking current medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
• Patients with known human immunodeficiency virus (HIV) are not eligible if cluster of differentiation (CD)4 count is =\< 200 cell/mm\^3 or if receiving antiretroviral therapy

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• ECOG-ACRIN Cancer Research Group: collaborator

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Gastrointestinal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms

Interventions

AMG 337; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lakshmi Rajdev

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: January 26, 2015
• Study Start: March 6, 2015
• Primary Completion: March 6, 2015
• Last Updated: May 25, 2023

Record last verified: 2023-05

Locations

US (1)