Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Sanofi
Roche/Genetech
City of Hope National Medical Center
Piedmont Hospital Research Institute
Medical College of Wisconsin
Queens Health Network
Weill Medical College of Cornell University
Memorial Cancer Institute, Florida
University of Pittsburgh
Long Island Jewish Medical Center
Nebraska Cancer Specialists Methodist Estabrook Cancer Center
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00515411
First received: August 10, 2007
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Junction Adenocarcinoma
Gastric Cancer
Drug: Docetaxel, Leucovorin, Fluorouracil, Cisplatin
Drug: Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Patients With Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary endpoints of efficacy are response rate, median PFS, overall, and 1 year survival. [ Time Frame: a year ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2006
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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).

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)
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

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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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. Patients with alkaline phosphatase elevation secondary to the bony metastases rather than liver dysfunction may proceed with treatment on protocol after discussion with the principal investigator.

  • 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.
  • Patients must have HER2-positive (FISH+ or IHC 3+) metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to be eligible for trastuzumab. For the purposes of this protocol, FISH+ is defined as HER2:CEP17 ratio ≥ 2.0. Biopsy samples with cohesive IHC3+ or FISH+ clones are considered HER2 positive irrespective of size, i.e.<10%. FISH+ defined as >2 HER2:CEP17.
  • Patients who are receiving trastuzumab must have a left ventricular ejection fraction of ≥ 50%.

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.
  • History of a stroke or CVA within 6 months
  • Clinically significant peripheral vascular disease.
  • Clinically significant hearing loss or ringing in the ears.
  • Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.
  • Inability to comply with study and/or follow-up procedures.
  • Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.
  • For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, prior trastuzumab treatment is not allowed.
  • For patients who are Her2 positive and will be treated on the trastuzumab+mDCF cohort, left ventricular function <50%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00515411

Contacts
Contact: Yelena Janjigian, MD 646-888-4186
Contact: David Kelsen, MD 646-888-4179

Locations
United States, California
City of Hope Cancer Center Active, not recruiting
Duarte, California, United States, 91010
United States, Florida
Memorial Cancer Institute Recruiting
Pembroke Pines, Florida, United States, 33025
Contact: Pablo Ferraro, MD    954-430-6868      
United States, Georgia
Piedmont Hospital Research Institute Recruiting
Atlanta, Georgia, United States, 30309
Contact: Charles Henderson, MD    404-350-9853      
United States, Nebraska
Nebraska Cancer Specialists, Methodist Estabrook Cancer Center Recruiting
Omaha, Nebraska, United States, 68114
Contact: Yungpo Bernard Su, MD    402-354-8124      
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Yelena Janjigian, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Yelena Janjigian, MD         
Queens Cancer Center of Queens Hospital Recruiting
Jamaica, New York, United States, 11432
Contact: Margaret Kemeny, MD    718-883-4031      
Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Bhoomi Mehrotra, MD    718-470-8934      
Weill Medical College of Cornell University Active, not recruiting
New York, New York, United States, 10021
Memorial Sloan-Kettering Cancer Center 1275 York Avenue Recruiting
New York, New York, United States, 10065
Contact: Yelena Janjigian, MD    646-888-4186      
Principal Investigator: Yelena Janjigian, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Yelena Janjigian, MD         
Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital Recruiting
Sleepy Hollow, New York, United States
Contact: Yelena Janjigian, MD         
United States, Ohio
University Hospital of Cleveland Active, not recruiting
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Ronald Stoller, MD    412-692-4724      
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Paul Ritch, MD    414-805-4600      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Sanofi
Roche/Genetech
City of Hope National Medical Center
Piedmont Hospital Research Institute
Medical College of Wisconsin
Queens Health Network
Weill Medical College of Cornell University
Memorial Cancer Institute, Florida
University of Pittsburgh
Long Island Jewish Medical Center
Nebraska Cancer Specialists Methodist Estabrook Cancer Center
Investigators
Principal Investigator: Yelena Janjigian, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00515411     History of Changes
Other Study ID Numbers: 06-103
Study First Received: August 10, 2007
Last Updated: March 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
gastroesophageal junction
gastric cancer
adenocarcinoma
unresectable gastric cancer
metastatic gastric

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Docetaxel
Cisplatin
Fluorouracil
Leucovorin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014