A Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Patients With Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel, Leucovorin, Fluorouracil, Cisplatin
- Conditions
- Gastroesophageal Junction Adenocarcinoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 111
- Locations
- 15
- Primary Endpoint
- 6 Month Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Chemotherapy given together is a standard way to treat your cancer. One standard treatment includes a combination of docetaxel, cisplatin, and fluorouracil. However, the original combination of these three drugs can cause many side effects. This study is being done to find out if these three drugs can be given at lower doses more often, with fewer side effects and still maintain the same benefit as the standard way of giving this three drug combination. If your tumor overexpresses a protein called Her2, you are also eligible to receive trastuzumab with chemotherapy. Trastuzumab is a medicine that has been approved by the US Food and Drug Administration for the treatment of Her2 positive breast cancer. Trastuzumab is now also a standard treatment in combination with chemotherapy for the treatment of Her2 positive stomach cancer. If your tumor is Her2 positive, you would receive the modified administration schedule of docetaxel, cisplatin, and fluorouracil with trastuzumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma may be classified according to Siewert's classification type I, II, or III\[43\].
- •Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease.
- •If no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (eg. PET/CT scan or MRI in addition to the CT scan). If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required.
- •Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease. Measurable disease is defined as that which can be measured in at least one dimension as \> 20 mm with conventional techniques, or \>10 mm by high resolution imaging. Disease that is identified on radiology studies, but does not meet the criteria for measurable disease, is considered non-measurable.
- •Patients may have received no prior chemotherapy for metastatic or unresectable disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration. Patients may not have received prior docetaxel or cisplatin.
- •Age 18 years or older.
- •Karnofsky performance status \> than or = to 70% (ECOG performance status 0-1).
- •Peripheral neuropathy \< than or = to grade
- •Hematologic (minimal values):
- •White blood cell count \> than or = to 3000/mm3
Exclusion Criteria
- •Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric or GEJ adenocarcinoma are ineligible.
- •Patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration. Patients must have recovered from adverse events from any previous therapy.
- •Patients who have received previous docetaxel or cisplatin.
- •Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
- •Patients with brain or central nervous system metastases, including leptomeningeal disease.
- •Pregnant (positive pregnancy test) or breast feeding.
- •Serious, non-healing wound, ulcer, or bone fracture.
- •Significant cardiac disease as defined as:
- •unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months
- •Evidence of bleeding diathesis or coagulopathy.
Arms & Interventions
Arm A, - Modified DCF
Drug Dose (mg/m2) Schedule Docetaxel 40 Day 1 IVPB (60 min) Leucovorin 400 Day 1 IVPB (30 min) Fluorouracil 400 IVP day 1 Fluorouracil 1000 mg/m2/d daily x 2 days Cisplatin 40 Day 2 OR 3 IVPB (30 min) Arm A is repeated every 2 weeks, and a cycle will be considered 6 weeks (eg 3 treatments).
Intervention: Docetaxel, Leucovorin, Fluorouracil, Cisplatin
ARM B - Parent DCF with G-CSF
Docetaxel 75 Day 1 IVPB (60 min) Cisplatin 75 Day 1 IVPB (60 min) Fluorouracil 750 IVCI daily x 5 days Neulasta 6 mg subcut on d 8, 9, or 10 or Neupogen 300 or 480 mcg\* subcut x 7 d 10-17 \* 300 mcg for weight \< 60 kg, 480 mcg for weight \> 60 kg
Intervention: Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen
Arm C - Modifid DCF + Trastuzumab
Treatment for Her2 Positive Participants Docetaxel 40 Day 1 IVPB (60 min) Leucovorin 400 Day 1 IVPB (30 min) Fluorouracil 400 IVP day 1 Fluorouracil 1000 mg/m2/d daily x 2 days Cisplatin 40 Day 2 OR 3 IVPB (30 min) Trastuzumab Administered on an every 2 week dosing schedule. Initial loading dose of 6 mg/kg over 90 minutes, followed by trastuzumab 4 mg/kg every 2 weeks over 30 minutes.
Intervention: Docetaxel, Leukvorin, Flurouracil, Cisplatin, Trastuzumab
Outcomes
Primary Outcomes
6 Month Progression Free Survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
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", or similar definition as accurate and appropriate
Secondary Outcomes
- Overall Survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 43 months)