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

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ClinicalTrials.gov Identifier: NCT02344810
Recruitment Status : Withdrawn (The study did not open to accrual. No start date and no completion dates.)
First Posted : January 26, 2015
Last Update Posted : October 19, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
ECOG-ACRIN Cancer Research Group
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

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.

Condition or disease Intervention/treatment Phase
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 Drug: c-Met inhibitor AMG 337 Other: placebo Drug: oxaliplatin Drug: leucovorin calcium Drug: fluorouracil Other: pharmacological study Other: laboratory biomarker analysis Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A Phase I and Randomized Phase II Double Blinded Placebo Controlled Study of mFOLFOX6 +/- AMG 337 in the First Line Treatment of Patients With Her2/Neu Negative and High MET Expressing Advanced Gastric and Esophageal Adenocarcinoma
Estimated Study Start Date : March 6, 2015
Estimated Primary Completion Date : March 6, 2018
Estimated Study Completion Date : March 6, 2020


Arm Intervention/treatment
Experimental: Arm A (AMG 337, mFOLFOX6)
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
Given PO
Other Names:
  • AMG 337
  • AMG337

Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP

Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV

Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies

Active Comparator: Arm B (placebo, mFOLFOX6)
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
Given PO
Other Name: PLCB

Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP

Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV

Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies




Primary Outcome Measures :
  1. 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) [ Time Frame: 28 days ]
  2. Progression-free survival (Phase II) [ Time Frame: Up to 2 years ]
    The study will have 90% power to detect the above improvement in PFS using a one-sided 0.10 level log rank test.


Secondary Outcome Measures :
  1. Overall survival (Phase II) [ Time Frame: Up to 2 years ]
  2. Response rate (Phase II) [ Time Frame: Up to 2 years ]
  3. Disease control rate (Phase II) [ Time Frame: Up to 2 years ]
  4. Incidence of toxicity graded according to CTCAE v.4 (Phase II) [ Time Frame: Up to 2 years ]
    The study will have at least 83% power to detect an absolute differences of 26% or more (e.g. 64% versus 38% true toxicity rates) between the two arms for any given adverse event, using a one-sided 5% level Fisher's exact test.

  5. Time to development of new metastasis (Phase II) [ Time Frame: Up to 2 years ]
  6. Evaluation of MET amplification via fluorescence in situ hybridization (FISH) (Phase II) [ Time Frame: Up to 2 years ]
  7. Evaluation of MET amplification and MET expression as determined by DAKO IHC (Phase II) [ Time Frame: Up to 2 years ]
    Comparison of DAKO IHC to Ventana IHC and comparison of amplification by FISH to overexpression by Ventana IHC amongst all pre-registered patients.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Patients must not have a pre-existing > grade 1 (Common Terminology Criteria for Adverse Events version 4 [CTCAEv4]) motor or sensory neuropathy
  • Patients must not have an uncontrolled infection, active hepatic, biliary disease or other uncontrolled intercurrent illnesses including, but not limited to: uncontrolled ascites, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive disorders that would limit compliance with study requirements
  • PHASE I:
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria within 4 weeks prior to registration; patients must not have clinical or radiographic evidence of brain metastasis
  • Patients must have histologically or cytologically confirmed adenocarcinoma originating from anywhere in the gastrointestinal tract
  • Patients must have progression on standard therapies, for which effective therapy is not available (or patients are not a candidate for or are intolerant of such therapies)
  • Patients must NOT have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:

    • Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ)
    • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years from registration
  • Patients may have received prior surgery or radiotherapy if > 4 weeks prior to registration and patient does not have any unresolved or unstable serious toxicity
  • Patients must not be receiving an investigational agent concurrently and must not have received any other investigational agents within 4 weeks prior to randomization
  • PHASE II:
  • Patients must have measurable disease by RECIST 1.1 criteria within 4 weeks prior to registration to Step 0; patients must not have clinical or radiographic evidence of brain metastasis because of their poor prognosis
  • Patient disease status must be as follows:

    • Adenocarcinoma or poorly differentiated carcinoma of the stomach, esophagus or gastroesophageal (GE) junction
    • Histologically or cytologically confirmed Her2/neu negative cancer prior to pre-registration; Her2/neu status must be determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
    • Locally advanced or metastatic disease that is inoperable and not amenable to curative therapy; linitis plastica is permitted
    • Patient must NOT have gastric carcinoid, sarcomas or squamous cell carcinoma
  • Patients may have received prior surgery or radiotherapy if > 4 weeks prior to registration to Step 0 and patient does not have any unresolved or unstable serious toxicity
  • Patients must NOT have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:

    • Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ)
    • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years from registration to Step 0
  • Patients must not be receiving an investigational agent concurrently and must not have received any other investigational agents within 4 weeks prior to registration to Step 0
  • Patient may not have received prior chemotherapy for advanced disease or prior oxaliplatin or anti-MET therapy
  • Previous neo-adjuvant or adjuvant treatment is allowed provided that it was discontinued >= 6 months prior to registration to Step 0
  • Patients must have paraffin-embedded tumor specimen available for submission for central determination of MET expression status

    • NOTE: it is recommended that patients not be pre-registered until the required tumor specimens are on hand and ready for submission; if submission of tissue will be submitted more than 5 working days after pre-registration, immediately notify the receiving laboratory
  • Patients must have had MET expression status determined by the Immunohistochemistry Laboratory and Image Analysis Laboratory in the Department of Pathology of The University of Texas MD Anderson Cancer Center in Houston: the report from the central laboratory indicates tumor tissue has MET

    • NOTE: for this protocol, 'MET High' will be defined as: >= 50% tumor cells with a staining intensity of 2+ or 3+ in IHC utilizing the CONFIRM anti-total MET, SP44, rabbit monoclonal primary antibody

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02344810


Locations
United States, Pennsylvania
ECOG-ACRIN Cancer Research Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
ECOG-ACRIN Cancer Research Group
Investigators
Principal Investigator: Lakshmi Rajdev ECOG-ACRIN Cancer Research Group

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT02344810     History of Changes
Other Study ID Numbers: EA2132
NCI-2014-01315 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA2132 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA2132 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: January 26, 2015    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Calcium, Dietary
Oxaliplatin
Fluorouracil
Levoleucovorin
Leucovorin
Bone Density Conservation Agents
Physiological Effects of Drugs
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents