Clinical Trials /

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

NCT00515411

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Study of Modified <span class="go-doc-concept go-doc-intervention">Docetaxel</span>, <span class="go-doc-concept go-doc-intervention">Cisplatin</span>, and <span class="go-doc-concept go-doc-intervention">Fluorouracil</span> (<span class="go-doc-concept go-doc-intervention">mDCF</span>) in Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

Title

  • Brief Title: Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
  • Official Title: A Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Patients With Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
  • Clinical Trial IDs

    NCT ID: NCT00515411

    ORG ID: 06-103

    Trial Conditions

    Gastroesophageal Junction Adenocarcinoma

    Gastric Cancer

    Trial Interventions

    Drug Synonyms Arms
    Docetaxel, Leucovorin, Fluorouracil, Cisplatin Arm A, - Modified DCF
    Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen ARM B - Parent DCF with G-CSF

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A, - Modified DCF Active Comparator 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). Docetaxel, Leucovorin, Fluorouracil, Cisplatin
    ARM B - Parent DCF with G-CSF Active Comparator 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 Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen

    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 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%

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    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.

    Secondary Outcome Measures

    Secondary endpoints of efficacy are response rate, median PFS, overall, and 1 year survival.

    Trial Keywords

    gastroesophageal junction

    gastric cancer

    adenocarcinoma

    unresectable gastric cancer

    metastatic gastric