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Adenocarcinoma of the EsophagusPhase 1/2NCT02344810

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

A Phase 1/2 study testing c-Met inhibitor AMG 337, oxaliplatin and leucovorin calcium in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Eastern Cooperative Oncology Group at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
c-Met inhibitor AMG 337, oxaliplatin and leucovorin calcium
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
6 Mar 2015to 6 Mar 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 44Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • ECOG-ACRIN Cancer Research Group

    Philadelphia, Pennsylvania, 19103

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the toxicity of combination therapy with AMG 337 (c-Met inhibitor AMG 337) and mFOLFOX6 (oxaliplatin, leucovorin calcium, and fluorouracil) chemotherapy in patients with advanced or metastatic gastrointestinal (GI) cancers. (Phase I) II. To determine the dose of AMG 337 to be used in combination with mFOLFOX6 chemotherapy in the phase II portion of the trial. (Phase I) III. To determine the pharmacokinetics of AMG 337 in combination with mFOLFOX6. (Phase I) IV. To determine if the addition of AMG 337 to mFOLFOX6 chemotherapy improves median progression-free survival (PFS) in the first line treatment of patients with human epidermal growth factor receptor 2 (Her2Neu) negative and high c-met proto-oncogene (MET) expressing advanced esophagogastric and gastroesophageal junction (GEJ) adenocarcinoma. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to overall survival (OS). (Phase II) II. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to response rate and disease control rate. (Phase II) III. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to toxicity rates. (Phase II) IV. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to time to development of new metastasis. (Phase II) V. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to evaluation of MET amplification. (Phase II) VI. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to evaluation of MET amplification and MET expression as determined by DAKO immunohistochemistry (IHC) for comparison to Ventana IHC. (Phase II) VII. To evaluate the addition of AMG 337 to mFOLFOX6 chemotherapy and also to evaluate the placebo/mFOLFOX6 chemotherapy combination in the first line treatment of patients with Her2Neu negative and high c-MET expressing advanced esophagogastric and GEJ adenocarcinoma, with regards to a retrospective re-evaluation of the cutpoint used by the computer algorithm for c-MET IHC to assess its ability to distinguish responding versus non-responding patients will be undertaken in this population, so that a potentially more optimal cutpoint to define high c-MET tumors in patients can be identified. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of c-Met inhibitor AMG 337 followed by a phase II study.

PHASE I: Patients receive c-Met inhibitor AMG 337 orally (PO) once daily (QD) on days 1-28; and oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM A: 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.

ARM B: 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.

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.

Being tested
c-Met inhibitor AMG 337, placebo, oxaliplatin, leucovorin calcium, fluorouracil
Medical subject headings
Adenocarcinoma Of Esophagus, Gastrointestinal Neoplasms, Esophageal Neoplasms, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • c-Met inhibitor AMG 337Drug

    Also called AMG 337, AMG337

    Given PO

  • placeboOther

    Also called PLCB

    Given PO

  • oxaliplatinDrug

    Also called 1-OHP, Dacotin, Dacplat, Eloxatin

    Given IV

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02344810
Study groupRoleWhat they receive
Arm A (AMG 337, mFOLFOX6)ExperimentalPatients 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.
Receives: 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 comparatorPatients 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.
Receives: Other: placebo; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 28 days

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (7)

  1. Overall survival (Phase II)

    Measured: Up to 2 years

  2. Response rate (Phase II)

    Measured: Up to 2 years

  3. Disease control rate (Phase II)

    Measured: Up to 2 years

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

    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.

    Measured: Up to 2 years

  5. Time to development of new metastasis (Phase II)

    Measured: Up to 2 years

  6. Evaluation of MET amplification via fluorescence in situ hybridization (FISH) (Phase II)

    Measured: Up to 2 years

  7. Evaluation of MET amplification and MET expression as determined by DAKO IHC (Phase II)

    Comparison of DAKO IHC to Ventana IHC and comparison of amplification by FISH to overexpression by Ventana IHC amongst all pre-registered patients.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2015 (estimated)
  2. Study start6 Mar 2015
  3. Primary completion6 Mar 2015

Why it stopped: The study did not open to accrual. No start date and no completion dates.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02344810
Sponsor's protocol ID
EA2132
Other IDs
NCI-2014-01315, EA2132, EA2132, U10CA180820
Status last verified
May 2023
First submitted
16 Jan 2015
Last updated
25 May 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing c-Met inhibitor AMG 337, oxaliplatin and leucovorin calcium in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Eastern Cooperative Oncology Group at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02344810.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2023.

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