Gastric Cancer Adenocarcinoma Metastatic
Conditions
Keywords
metastatic gastric or adenocarcinoma of the GE junction
Brief summary
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
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.
Interventions
DRUGDocetaxel
Taxotere 60 mg/m2 as an intravenous (IV) infusion over 1 hour
DRUGcetuximab
ERBITUX 400 mg/m2 IV over 120 minutes (first dose only), all other doses are 250 mg/m2 over 60 minutes.
DRUGoxaliplatin
Eloxatin 130 mg/m2 IV over 2 hours
Sponsors
Eli Lilly and Company
Sanofi
US Oncology Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Treatment will continue until disease progression or intolerable toxicity, up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Treatment will continue until disease progression or intolerable toxicity | 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. |
| Objective Response Rate (ORR) | Treatment will continue until disease progression or intolerable toxicity. | 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. |
| Time to Response | Treatment will continue until disease progression or intolerable toxicity | 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. |
| Duration of Response | Treatment will continue until disease progression or intolerable toxicity | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DOCOX Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 every 21 days | 75 |
| DOCOX+Cebuximab Docetaxel 60 mg/m2 + Oxaliplatin 130 mg/m2 + Cetuximab 400 mg/m2 (first dose only, subsequent doses 250 mg/m2) every 21 days | 75 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 34 |
| Overall Study | Disease Progression | 39 | 32 |
| Overall Study | Investigator Request | 5 | 3 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Patient Request | 6 | 5 |
Baseline characteristics
| Characteristic | DOCOX | DOCOX+Cebuximab | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 10.9 | 61.5 years STANDARD_DEVIATION 11.5 | 61.0 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Asian | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Black | 5 participants | 7 participants | 12 participants |
| Race/Ethnicity, Customized Caucasian | 62 participants | 56 participants | 118 participants |
| Race/Ethnicity, Customized Hawaiian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants | 9 participants | 14 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 75 participants | 75 participants | 150 participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 59 Participants | 60 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 68 | 67 / 72 |
| serious Total, serious adverse events | 20 / 68 | 26 / 72 |
Outcome results
Primary
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.
Time frame: Treatment will continue until disease progression or intolerable toxicity, up to 2 years
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DOCOX | Progression-free Survival | 4.7 months |
| DOCOX+Cebuximab | Progression-free Survival | 5.1 months |
Secondary
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.
Time frame: Treatment will continue until disease progression or intolerable toxicity
Population: Patients who achieve a major objective response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DOCOX | Duration of Response | 7.3 months |
| DOCOX+Cebuximab | Duration of Response | 5.6 months |
Secondary
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.
Time frame: Treatment will continue until disease progression or intolerable toxicity.
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOCOX | Objective Response Rate (ORR) | 26.5 percentage of participants |
| DOCOX+Cebuximab | Objective Response Rate (ORR) | 38.0 percentage of participants |
Secondary
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.
Time frame: Treatment will continue until disease progression or intolerable toxicity
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DOCOX | Overall Survival | 8.5 months |
| DOCOX+Cebuximab | Overall Survival | 9.4 months |
Secondary
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.
Time frame: Treatment will continue until disease progression or intolerable toxicity
Population: Patients who achieve a major objective response (CR or PR)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DOCOX | Time to Response | 1.3 months |
| DOCOX+Cebuximab | Time to Response | 1.4 months |