Docetaxel+Oxali+/-Cetux Met Gastric/GEJ

Study Overview
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Brief Summary
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The purpose of this research study is to find out what effects (good and bad) docetaxel, oxaliplatin, and cetuximab have on gastric or GEJ cancer.

Detailed Description
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This is a Phase II, open- label, randomized, noncomparative study. Patients will be stratified at randomization by ECOG PS. There is no intent to have equal numbers of patients for each PS (ie, 0, 1, and 2), but rather stratification will be conducted to ensure that the 2 treatment arms are well-balanced for ECOG PS. Patients will be randomly assigned to either Arm 1 - Taxotere 60 mg/m2 as an intravenous (IV) infusion over 1 hour, followed by Eloxatin 130 mg/m2 IV over 2 hours or Arm 2 - Taxotere 60 mg/m2 as an IV infusion over 1 ho ur, followed by Eloxatin 130mg/m2 IV over 2 hours, followed by ERBITUX 400 mg/m2 IV over 120 minutes (first dose only), all other doses are 250 mg/m2 over 60 minutes. Taxotere and Eloxatin will be given on Day 1 of each 21-day cycle; ERBITUX is given on Days 1, 8, and 15 of each cycle. Treatment will continue until disease progression or intolerable toxicity. Patients who achieve a CR will receive an additional 2 cycles of treatment. Patients will be limited to 24 months of participation, counted from the date of the first dose of study drug.

Official Title
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Phase II Trial of Docetaxel Plus Oxaliplatin (DOCOX) With or Without Cetuximab in Patients With Metastatic Gastric and/or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Cancer Adenocarcinoma Metastatic

Intervention / Treatment
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* Drug: Docetaxel
* Drug: cetuximab
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has histologically confirmed Stage IV adenocarcinoma of the GEJ/stomach Note: Adjuvant radiation plus treatment with 5-FU and leucovorin is permitted, but not required. Patients must have measurable disease Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 Patient is greater than 18 years of age If present, any pre-existing (current) peripheral neuropathy must be ≤ Grade 1 Patient's laboratory values must fall within the limits set forth in section 4.2 of the protocol Patient has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential) If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a 2 month period thereafter Patient (or guardian) has signed a Patient Informed Consent Form Patient (or guardian) has signed a Patient Authorization Form Exclusion Criteria: Patient has any metastatic disease other than that defined in section 4.2 (criterion #1) Patient has had prior treatment that included anything other than adjuvant radiation plus treatment with 5-FU and leucovorin. Prior treatment must have been completed > 6 months prior to registration in current study. No other prior regimens are allowed. Note: Adjuvant radiation plus treatment with 5-FU and leucovorin is permitted, but not required. If present, any peripheral neuropathy is > Grade 1 Patient has a known hypersensitivity to Taxotere (or any drug formulated with Polysorbate-80), or Eloxatin Has had a prior severe infusion reaction (Grade 4) to a monoclonal antibody Has received prior therapy, at any time, which specifically and directly targets the EGFR pathway Patient is receiving concurrent immunotherapy or any other concurrent treatment for their cancer Has had prior stem cell or bone marrow transplant or any organ transplant with the exception of corneal transplant or cadaver bone graft Has a significant history of uncontrolled cardiac disease; ie, uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction (LVEF<50%) Has evidence of CNS involvement (CNS imaging is not required for study enrollment unless clinically suspected CNS disease is present.) Patient has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection Patient is known to be HIV positive or have a history of hepatitis B or C Patient has a history of other malignancy within the last 5 years (except for squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix , or superficial transitional cell carcinoma of the bladder), which could affect the diagnosis or assessment of current condition. Patient is a pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1- Docetaxel plus Oxaliplatin<br>Docetaxel as an intravenous (IV) infusion over 1 hour, followed by oxaliplatin IV over 2 hours | Drug: Docetaxel<br>* Taxotere 60 mg/m2 as an intravenous (IV) infusion over 1 hour<br>* Other names: Taxotere (docetaxel);Drug: oxaliplatin<br>* Eloxatin 130 mg/m2 IV over 2 hours<br>* Other names: Eloxatin (oxaliplatin);|
| Active Comparator: 2- Docetaxel plus oxaliplatin plus cetuximab<br>Docetaxel 60 mg/m2 as an IV infusion over 1 ho ur, followed by oxaliplatin 130 mg/m2 IV over 2 hours, followed by cetuximab 400 mg/m2 IV over 120 minutes (first dose only), all other doses are 250 mg/m2 over 60 minutes. | Drug: Docetaxel<br>* Taxotere 60 mg/m2 as an intravenous (IV) infusion over 1 hour<br>* Other names: Taxotere (docetaxel);Drug: cetuximab<br>* ERBITUX 400 mg/m2 IV over 120 minutes (first dose only), all other doses are 250 mg/m2 over 60 minutes.<br>* Other names: ERBITUX (cetuximab);Drug: oxaliplatin<br>* Eloxatin 130 mg/m2 IV over 2 hours<br>* Other names: Eloxatin (oxaliplatin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Treatment will continue until disease progression or intolerable toxicity, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. | Treatment will continue until disease progression or intolerable toxicity | 
| Objective Response Rate (ORR) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. | Treatment will continue until disease progression or intolerable toxicity. | 
| Time to Response | For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response. | Treatment will continue until disease progression or intolerable toxicity | 
| Duration of Response | The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. | Treatment will continue until disease progression or intolerable toxicity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic gastric or adenocarcinoma of the GE junction