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A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
Not Recruiting
Trial ID: NCT01641939
Purpose
This multicenter, randomized, adaptive Phase II/III study will evaluate the efficacy and
safety of trastuzumab emtansine (T-DM1) compared to standard taxane (docetaxel or paclitaxel)
treatment in participants with human epidermal growth factor receptor 2 (HER2)-positive
advanced gastric cancer. At the start of the trial (stage 1), participants will be randomized
with a ratio 2:2:1 to one of three treatment arms: Arm A: trastuzumab emtansine 3.6 milligram
per kilogram (mg/kg) per intravenous injection (IV) every 3 weeks; Arm B: trastuzumab
emtansine 2.4 mg/kg IV every week; Arm C: standard taxane therapy (docetaxel 75 milligram per
meter square [mg/m^2] IV every 3 weeks or paclitaxel 80 mg/m^2 kg IV every week per
investigator choice). At the end of the first stage of the study, the dose and schedule of
trastuzumab emtansine that will be used in the second stage of the study will be selected by
an Independent Data Monitoring Committee (IDMC). The regimen selection analysis will be made
after approximately 100 participants across all three study arms have been treated for at
least 12 weeks.
Once a trastuzumab emtansine regimen has been selected, Stage I participants who were
assigned to the treatment arm which was selected for Stage II of the study and participants
who were in the standard taxane group will continue to receive their assigned treatment
regimen. Stage I participants who were assigned to the regimen that was not selected for
further evaluation will continue to receive their assigned regimen and will continue to be
followed for efficacy and safety. In Stage II of the study, additional participants will be
recruited and randomized with a ratio 2:1 to either the selected regimen of trastuzumab
emtansine or to the standard taxane therapy. Participants will receive study treatment until
disease progression, unacceptable toxicity, initiation of another cancer therapy or
withdrawal.
Official Title
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
Eligibility
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 12 weeks from the first dose of study treatment
- Measurable and/or evaluable disease based on Response Evaluation Criteria in Solid
Tumors (RECIST version 1.1)
- Adequate organ function as determined by the following laboratory results, within 28
days prior to randomization
- Participants must have a history of advanced gastric cancer (AGC), defined as
unresectable and locally advanced or metastatic gastric cancer, including
adenocarcinoma of the gastroesophageal junction (GEJ), and must have experienced
disease progression during or after first-line therapy for their disease
- HER2-positive tumor (primary tumor or metastatic lesion) as confirmed by central
laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
- Participants must have received at least one prior chemotherapy regimen for AGC; prior
therapy does not need to have included HER2-directed therapy.
- First-line therapy for AGC, including adenocarcinoma of the GEJ, must have included a
combination of at least a platinum- and a fluoropyrimidine-based treatment given
concurrently; prior therapy does not need to have included a HER2-directed therapy.
- Adjuvant or neoadjuvant therapy for AGC is allowed.
Exclusion Criteria:
- An interval shorter than 21 days from the last dose of chemotherapy or HER2-directed
therapy until the time of randomization
- Prior treatment with trastuzumab emtansine, docetaxel, or paclitaxel either as single
agents or as part of a treatment regimen.
- Treatment with any investigational anticancer drug within 21 days of the first study
treatment administration
- More than one prior line of therapy for advanced gastric cancer
- History of other malignancy within the previous 5 years except for appropriately
treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine
cancer, or other malignancies with an expected curative outcome
- Brain metastases that are untreated or symptomatic or require any radiation, surgery,
or steroid therapy to control symptoms from brain metastases within 1 month of
randomization
- Peripheral neuropathy Grade >/=2
- Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, serious cardiac
arrhythmia)
- Other current, severe, uncontrolled systemic disease (e.g., clinically significant
metabolic disease, wound healing disorders, ulcers)
- Clinically significant bleeding within 30 days before enrollment
- For female participants, current pregnancy or lactation
- Major surgical procedure or significant traumatic injury within 28 days prior to
randomization or anticipation of the need for major surgery during the course of study
treatment
- Infection with Human immunodeficiency virus (HIV) or hepatitis B virus, hepatitis C
virus
Intervention(s):
drug: trastuzumab emtansine
drug: trastuzumab emtansine
drug: taxane
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
CCTO
650-498-7061