A Study of Trastuzumab Emtansine Versus Taxane in Patients With Advanced Gastric Cancer

This study is currently recruiting participants.
Verified April 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01641939
First received: July 13, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

This multicenter, randomized, adaptive Phase II/III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) compared to standard taxane treatment in patients with HER2-positive advanced gastric cancer. At the start of the trial, patients will be randomized to one of three treatment arms: Arm A: trastuzumab emtansine 3.6 mg/kg every 3 weeks; Arm B: trastuzumab emtansine 2.4 mg/kg every week; Arm C: standard taxane therapy (docetaxel or paclitaxel 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. The regimen selection analysis will be made after approximately 100 patients across all three study arms have been treated for at least 4 cycles (12 weeks).

Once a trastuzumab emtansine regimen has been selected, Stage I patients who were assigned to the treatment arm which was selected for Stage II of the study and patients who were in the standard taxane group will continue to receive their assigned treatment regimen. Stage I patients 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 patients will be recruited and randomized to either the selected regimen of trastuzumab emtansine or to the standard taxane therapy. Patients will receive study treatment until disease progression, unacceptable toxicity or withdrawal.


Condition Intervention Phase
Gastric Cancer
Drug: trastuzumab emtansine
Drug: taxane
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Duration of response (DOR) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Safety: incidence of adverse events [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Response distribution of treatment-related symptoms as measured by patient-reported outcome data [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Time to gastric cancer symptom progression as measured by the European Organization for Research and Treatment of Cancer questionnaire (EORTC QLQ-STO22) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Quality of life as measured by the European Organization for Research and Treatment of Cancer questionnaire (EORTC QLQ C30) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: serum concentration-time profile of trastuzumab emtansine [ Time Frame: Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: serum concentration-time profile of total trastuzumab [ Time Frame: Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: plasma concentration-time profile of DM1 [ Time Frame: Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 412
Study Start Date: September 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: trastuzumab emtansine 3.6 mg Drug: trastuzumab emtansine
trastuzumab emtansine 3.6 mg/kg every 3 weeks
Experimental: trastuzumab emtansine 2.4 mg Drug: trastuzumab emtansine
trastuzumab emtansine 2.4 mg/kg once a week
Active Comparator: Standard taxane therapy Drug: taxane
Standard taxane (docetaxel or paclitaxel) according to investigator choice

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, aged >/= 18 years
  • 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 v1.1)
  • Adequate organ function as determined by the following laboratory results, within 28 days prior to randomization
  • Patients 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)
  • Patients 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 patients, 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 HIV or hepatitis B virus, hepatitis C virus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01641939

Contacts
Contact: Reference Study ID Number: BO27952 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Show 149 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01641939     History of Changes
Other Study ID Numbers: BO27952, 2012-000660-22
Study First Received: July 13, 2012
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Taxane
Trastuzumab
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014