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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 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: August 26, 2014
Last verified: August 2014
  Purpose

This multicenter, randomized, adaptive Phase II/III study will evaluate the effi cacy and safety of trastuzumab emtansine (T-DM1) compared to standard taxane tre atment in patients with HER2-positive advanced gastric cancer. At the start of t he trial, patients will be randomized to one of three treatment arms: Arm A: tra stuzumab 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 inves tigator choice). At the end of the first stage of the study, the dose and schedu le of trastuzumab emtansine that will be used in the second stage of the study w ill 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 cycle s (12 weeks). Once a trastuzumab emtansine regimen has been selected, Stage I p atients who were assigned to the treatment arm which was selected for Stage II o f 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 receiv e their assigned regimen and will continue to be followed for efficacy and safet y. In Stage II of the study, additional patients will be recruited and randomize d to either the selected regimen of trastuzumab emtansine or to the standard tax ane therapy. Patients will receive study treatment until disease progression, un acceptable toxicity or withdrawal.


Condition Intervention Phase
Gastric Cancer
Drug: taxane
Drug: trastuzumab emtansine
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: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard taxane therapy Drug: taxane
Standard taxane (docetaxel or paclitaxel) according to investigator choice
Experimental: trastuzumab emtansine 2.4 mg Drug: trastuzumab emtansine
trastuzumab emtansine 2.4 mg/kg once a week
Experimental: trastuzumab emtansine 3.6 mg Drug: trastuzumab emtansine
trastuzumab emtansine 3.6 mg/kg every 3 weeks

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 152 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: August 26, 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
Trastuzumab
Taxane
Ado-trastuzumab emtansine
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 September 18, 2014