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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01641939
First received: July 13, 2012
Last updated: April 2, 2016
Last verified: April 2016
  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: taxane
Drug: trastuzumab emtansine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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 ]

Enrollment: 415
Study Start Date: September 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 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   (Adult, Senior)
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

  Hide Study Locations
Locations
United States, California
Bakersfield, California, United States, 93309
Stanford, California, United States, 94305-5151
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, Kansas
Westwood, Kansas, United States, 66205
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, New York
New York, New York, United States, 10065
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
Houston, Texas, United States, 77030
Argentina
Buenos Aires, Argentina, C1264AAA
Buenos Aires, Argentina, 1025
Rosario, Argentina, S2000KZE
Belgium
Leuven, Belgium, 3000
Brazil
Rio de Janeiro, RJ, Brazil, 20560-120
Porto Alegre, RS, Brazil, 90430-090
Porto Alegre, RS, Brazil, 90610-000
Barretos, SP, Brazil, 14784-400
Jau, SP, Brazil, 17210-080
Sao Paulo, SP, Brazil, 01246-000
Sorocaba, SP, Brazil, 18030-245
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Brampton, Ontario, Canada, L6R 3J7
Toronto, Ontario, Canada, M5B 1W8
Toronto, Ontario, Canada, M4C 3E7
China
Beijing, China, 100071
Beijing, China, 100142
Changchun, China, 130012
Changchun, China, 130021
Changzhou, China, 213003
ChongQing, China, 400042
Fuzhou, China, 350014
Guangzhou, China, 510060
Hangzhou, China, 310016
Harbin, China, 150081
Nanjing, China
Nanjing, China, 210009
Nantong, China, 226001
Shanghai, China, 200032
Shanghai, China, 200080
Shenyang, China, 110016
Wuhan, China, 430023
Xi'an, China, 710061
Xuzhou, China, 221004
Czech Republic
Hradec Kralove, Czech Republic, 500 05
Olomouc, Czech Republic, 775 20
Praha 2, Czech Republic, 128 08
Praha 5, Czech Republic, 150 06
Finland
Tampere, Finland, 33520
France
Brest, France, 29200
Clichy, France, 92118
Montpellier, France, 34298
Paris, France, 75571
Paris, France, 75908
Reims, France, 51092
Toulouse, France, 31059
Germany
Berlin, Germany, 10117
Dresden, Germany, 01307
Hamburg, Germany, 20249
Köln, Germany, 50937
Landshut, Germany, 84028
Magdeburg, Germany, 39104
Guatemala
Guatemala, Guatemala, 01010
Guatemala City, Guatemala, 01015
Hungary
Budapest, Hungary, 1097
Szeged, Hungary, 6720
Szolnok, Hungary, 5004
Zalaegerszeg, Hungary, 8900
Italy
Catanzaro, Calabria, Italy, 88100
Bologna, Emilia-Romagna, Italy, 40138
Torino, Piemonte, Italy, 10126
Firenze, Toscana, Italy, 50139
Pisa, Toscana, Italy, 56100
Japan
Aichi, Japan, 464-8681
Chiba, Japan, 260-8717
Chiba, Japan, 277-8577
Ehime, Japan, 791-0280
Hokkaido, Japan, 060-8648
Hyogo, Japan, 663-8501
Hyogo, Japan, 673-8558
Ibaraki, Japan, 309-1793
Miyagi, Japan, 980-8574
Osaka, Japan, 565-0871
Osaka, Japan, 589-8511
Saitama, Japan, 362-0806
Shizuoka, Japan, 411-8777
Shizuoka, Japan, 420-8527
Tochigi, Japan, 320-0834
Tokyo, Japan, 113-8677
Tokyo, Japan, 105-8470
Tokyo, Japan, 104-0045
Tokyo, Japan, 135-8550
Korea, Republic of
Seoul, Korea, Republic of, 05505
Seoul, Korea, Republic of, 06351
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 136-705
Seoul, Korea, Republic of, 137-807
Seoul, Korea, Republic of, 03080
Malaysia
Kuala Lumpur, Malaysia, 59100
Sabah, Malaysia, 88996
Mexico
Aguascalientes, Mexico, 20230
Chihuahua, Mexico, 31000
Mexico DF, Mexico, 06726
Panama
Panama City, Panama, 0832-00752
Peru
Chiclayo, Peru, CIX
Cusco, Peru, 08006
Jesus Maria, Peru, Lima 11
Lima, Peru, 34
Philippines
Cebu, Philippines, 6000
Quezon City, Luzon, Philippines, 1101
Poland
Gdansk, Poland, 80-952
Krakow, Poland, 31-501
Poznan, Poland, 61-866
Rybnik, Poland, 44-200
Warszawa, Poland, 02-781
Romania
Bucharest, Romania, 022328
Cluj-Napoca, Romania, 400015
Cluj-Napoca, Romania, 400058
Targu Mures, Romania, 540141
Russian Federation
Arkhangelsk, Russian Federation, 163045
Ivanovo, Russian Federation, 153040
Omsk, Russian Federation, 644013
Pyatigorsk, Russian Federation, 357502
Tula, Russian Federation, 300053
Singapore
Singapore, Singapore, 169610
Spain
Oviedo, Asturias, Spain, 33011
Santander, Cantabria, Spain, 39008
Santiago de Compostela, La Coruña, Spain, 15706
Barcelona, Spain, 08036
Madrid, Spain, 28046
Madrid, Spain, 28007
Sevilla, Spain, 41013
Zaragoza, Spain, 50009
Taiwan
Kaohsung, Taiwan, 883
Taipei, Taiwan, 100
Taoyuan, Taiwan, 333
Turkey
Erzurum, Turkey, 25240
Istanbul, Turkey, 34300
Istanbul, Turkey, 34890
Izmir, Turkey, 35100
Sıhhiye, ANKARA, Turkey, 06100
United Kingdom
Cardiff, United Kingdom, CF14 2TL
Glasgow, United Kingdom, G12 0YN
London, United Kingdom, SW3 6JJ
Manchester, United Kingdom, M2O 4BX
Sutton, United Kingdom, SM2 5PT
Weston Super Mare, United Kingdom, BS23 4TQ
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

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 2, 2016
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
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2016