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A RANDOMIZED, MULTICENTER, ADAPTIVE PHASE II/III STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TRASTUZUMAB EMTANSINE (T-DM1) VERSUS TAXANE (DOCETAXEL OR PACLITAXEL) IN PATIENTS WITH PREVIOUSLY TREATED LOCALLY ADVANCED OR METASTATIC HER2-POSITIVE GASTRIC CANCER, INCLUDING ADENOCARCINOMA OF THE GASTROESOPHAGEAL JUNCTION

Conditions

Adenocarcinoma of the Gastroesophageal Junction | Esophagus | Gastric Cancer | Stomach

Trial Phase

Phase II-III

Trial Purpose and Description

Trial Purpose

Trastuzumab emtansine is an investigational drug being studied by F. Hoffmann La Roche Ltd (Roche) and Yale Cancer Center for treating advanced gastric cancer. Trastuzumab emtansine is composed of a chemotherapeutic agent (DM1) linked to Herceptin® (trastuzumab), a monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer) that attaches to protein called HER2 on cancer cells. Trastuzumab emtansine has caused cancer cells to die in laboratory studies and has slowed tumor growth in animal studies. In clinical trials, some patients given trastuzumab emtansine experienced tumor shrinkage. Trastuzumab emtansine is produced by Roche. The use of trastuzumab emtansine in this research study is experimental, which means that it is not approved for the treatment of HER2 positive advanced gastric cancer or adenocarcinoma of the gastroesophageal junction.


Participation Guidelines

Age:
18 Years and older
Gender:
Both

Eligibility Criteria

  1. Patients must have a history of histologically or cytologically confirmed AGC and must have experienced documented objective radiographic or pathologic disease progression during or after first-line therapy for their disease.
  2. HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ alone or IHC 2+ in combination with ISH+, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment. ISH positivity is defined as a ratio of &ge2.0 for the number of HER2 gene copies to the number of signals for CEP17.
    1. Archival tumor samples obtained from primary or metastatic sites (original diagnostic specimens) are preferred.
    2. The block or slides should include a representative part of the tumor with an invasive tumor area for central confirmation of HER2 status.
    3. If formalin-fixed paraffin-embedded (FFPE) tissue blocks (or partial block) are unavailable due to country or site regulations, a minimum of 8 freshly cut unstained slides MUST be available for central review of HER2 status and up to 5 additional slides for mandatory biomarker research, if sufficient tissue is available.
  3. Patients must have received at least one prior chemotherapy regimen for AGC prior therapy does not need to have included HER2-directed therapy.
  4. Adjuvant or neoadjuvant chemotherapy or chemoradiation therapy for AGC is allowed.
    1. Patients whose AGC progresses or recurs in less than 6 months after completion of their adjuvant or neoadjuvant therapy are allowed to participate. In these cases, the adjuvant or neoadjuvant therapy will count as one prior therapy.

General inclusion criteria

  1. Age &ge 18 years
  2. ECOG performance status of 0 or 1.
  3. Life expectancy of at least 12 weeks from the first dose of study treatment
  4. Adequate organ function as determined by the following laboratory results, within 14 days prior to randomization
    1. Neutrophils &ge 1500 cells/mm3
    2. Platelets &ge 100,000 cells/mm3
    3. Hemoglobin &ge 9.0 g/dL patients may receive red blood cell transfusions to attain this concentration
    4. Serum creatinine &le 1.5 times the upper limit of normal (ULN)
    5. INR < 1.5 and aPTT < 1.5 × ULN (unless on therapeutic anticoagulation medication)
    6. Serum AST or ALT < 2.5 × ULN if bone metastases are present and alkaline phosphatase > 2.5 × ULN, AST and ALT must be < 1.5 × ULN
    7. Serum alkaline phosphatase may be > 2.5 × ULN only if bone metastases are present and both AST and ALT < 1.5 × ULN
    8. Serum total bilirubin < 1.5 × ULN. Patients with increased total bilirubin > 1.5 × ULN due to Gilbert&rsquos syndrome are allowed if the direct (conjugated) bilirubin level is within normal limits.
  5. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, specifically including protocol specified pharmacokinetic (PK) sampling.
    1. Pregnancy test if the patient is of childbearing potential (including premenopausal women who have had a tubal ligation)
    2. a) A serum ß-human chorionic gonadotropin (ß-HCG) pregnancy test must be performed at screening for women of childbearing potential, and for all women not meeting the definition of postmenopausal (&ge 12 months of amenorrhea) and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy.
      1. Patients with a negative serum pregnancy test but a positive urine pregnancy test are not eligible.
    3. Subsequent tests will be urine pregnancy tests. Any positive urine pregnancy test result must be confirmed by a serum ß-HCG test.
    4. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential.
  6. Women of childbearing potential and men with partners of childbearing potential must be willing to use a highly effective, non-hormonal form of contraception or two effective forms of contraception by the patient and/or partner and continue its use for the duration of study treatment and for 6 months after the last dose of study treatment.
Sponsor:
Genentech, Inc.
Dates:
01/11/2013
Last Updated:
Study HIC#:
1209010816