Official Title: “A Random Assignment Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) With Growth Factor Support in Patients With Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma”

Combination chemotherapy given together is a standard way to treat 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 performed to find out if these three drugs can be given more safely and with fewer side effects and still maintain the same survival rate benefit as the standard way of giving this three drug combination.

The investigators can reduce side effects by giving chemotherapy with medicine to boost the infection fighting cells during treatment. The investigators can also give lower doses of the chemotherapy more often. At this time, the investigators do not know which way the treatment works best. The investigators therefore wish to study both of these options. This trial will be a randomized trial, which means that if the patient agrees to participate in the trial, he/she will be assigned by random selection (such as in a flip of a coin) to receive either the original schedule of docetaxel, cisplatin, and fluorouracil with the addition of a medicine to boost the immune system, or lower and more frequent doses of docetaxel, cisplatin, and fluorouracil.

Neither the patient nor the doctor will be able to select which arm of the study the patient is assigned to. This is an open-label trial, which means that both the patient and the doctor will be informed of which treatment arm the patient is receiving.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2010

To determine the efficacy of modified docetaxel, cisplatin, and fluorouracil (mDCF) (ARM A) and the efficacy of parent DCF with growth factor support (ARM B) in patients with unresectable or metastatic gastric or gastroesophageal junction(GEJ) adenocarcinoma as measured by 6 month progression free survival (PFS). To establish the safety of mDCF and parent DCF with growth factor support in patients with unresectable or metastatic gastric or GEJ adenocarcinoma.

To observe other measures of efficacy of mDCF and parent DCF with growth factor support, including response rate, median PFS, overall and 1-year survival in patients with unresectable or metastatic gastric or GEJ adenocarcinoma. To explore the association of early FDG-PET imaging with treatment efficacy. To explore the differences in docetaxel pharmacology between both study arms. To bank tumor biopsy material for future planned correlative studies for association with chemotherapy efficacy and survival.

Intervention(s) in this Clinical Trial

• Drug: Docetaxel, Leucovorin, Fluorouracil, Cisplatin
  • 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 IVCI x 48 hours Cisplatin 40 Day 2 OR 3 IVPB (30 min)
• Drug: Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen
  • Drug Dose (mg/m2) Schedule 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 Arm B is repeated every 3 weeks, and a cycle will be considered every 6 weeks (eg 2 treatments). Tumor assessments will be performed following the completion of every cycle for the first 6 cycles, and then every 2 cycles thereafter.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 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 IVCI x 48 hours 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).
• Active Comparator: 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

Primary Measures

• The primary endpoint for both arms is progression free survival (PFS), as measured from the start of the treatment to the date of either documentation of disease progression or death.
  • Time Frame: progression or death
    Safety Issue?: No

Secondary Measures

• Secondary endpoints of efficacy are response rate, median PFS, overall, and 1 year survival.
  • Time Frame: a year
    Safety Issue?: No

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 1.
• Hematologic (minimal values):
• White blood cell count > than or = to 3000/mm3
• Absolute neutrophil count > than or = to 1500 cells/ mm3
• Hemoglobin > than or = to 9.0 g/dl
• Platelet count > than or = to 100,000 / mm3
• Hepatic (minimal values):
• Total bilirubin < or = to 1.5
• * AST and ALT and Alkaline phosphatase must be within the eligible range. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used.
• Kidney function (minimal values):
• Serum creatinine < than or = to 1.5 mg/dl - if serum creatinine is 1.2-1.5 mg/dl, the creatinine clearance (either measured or calculated) must be 50 ml/min or greater
• The patient has a PT (INR) < than or = to 1.5 and an PTT < than or = to 3 seconds above the upper limits of normal if the patient is not on anticoagulation. If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
• The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin
• The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
• Women of childbearing potential have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy.

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Manish Shah, MD Principal Investigator Memorial Sloan-Kettering Cancer Center  

Overall Contact: Manish Shah, MD (212) 639-3113 shah1@mskcc.org

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00515411

Study ID Number: 06-103

ClinicalTrials.gov Identifier: NCT00515411

Health Authority: United States: Institutional Review Board

Memorial Sloan-Kettering Cancer Center