Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

For female participants, current pregnancy or lactation
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
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

Intervenciones

drug

Taxane

Standard taxane (docetaxel 75 mg/m\^2 IV every 3 weeks or paclitaxel 80 mg/m\^2) IV once a week according to investigator choice.

drug

trastuzumab emtansine

trastuzumab emtansine 3.6 mg/kg IV every 3 weeks

drug

trastuzumab emtansine

trastuzumab emtansine 2.4 mg/kg IV once a week

Ubicaciones

Fundación Investigar

Buenos Aires, Argentina

Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología

Buenos Aires, Argentina

Instituto de Oncología de Rosario

Rosario, Argentina

Patrocinadores

PrincipalHoffmann-La Roche