A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
- Conditions
- Gastric Cancer
- Interventions
- Registration Number
- NCT01896531
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy of ipatasertib in combination with oxaliplatin, 5-fluorouracil, and leucovorin (modified FOLFOX6 \[mFOLFOX6\]) chemotherapy in participants with advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer. Participants will be randomized to receive either ipatasertib or placebo orally daily on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6 on Day 1 of each cycle.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically documented, inoperable locally advanced or metastatic or recurrent gastric/GEJ adenocarcinoma, not amenable to curative therapy
- Measurable disease, according to RECIST v1.1
- Life expectancy greater than or equal to (>/=) 12 weeks
- Adequate hematologic and organ function
- Previous chemotherapy for inoperable locally advanced or metastatic gastric/GEJ adenocarcinoma. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced gastric/GEJ adenocarcinoma, provided all treatments were completed >/= 6 months prior to randomization.
- Known human epidermal growth factor receptor 2 (HER2)-positive gastric/GEJ adenocarcinoma
- Radiation treatment within 28 days of randomization. Participants who have received palliative radiation treatment to peripheral sites (eg, bone metastases) within 28 days of randomization may be enrolled in the study if they have recovered from all acute, reversible effects and with notification of the Medical Monitor.
- Previous therapy for gastric/GEJ adenocarcinoma with Akt, phosphatidylinositol 3-kinase (PI3K), and/or mammalian target of rapamycin (mTOR) inhibitors
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ipatasertib + mFOLFOX6 Ipatasertib Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Ipatasertib + mFOLFOX6 Leucovorin Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Ipatasertib + mFOLFOX6 5-Fluorouracil Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Placebo + mFOLFOX6 Placebo Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Ipatasertib + mFOLFOX6 Oxaliplatin Participants will receive oral ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Placebo + mFOLFOX6 5-Fluorouracil Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Placebo + mFOLFOX6 Leucovorin Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle. Placebo + mFOLFOX6 Oxaliplatin Participants will receive the placebo equivalent to ipatasertib on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, assessed up to approximately 1.75 years PFS was defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST Version 1.1 and assessed by the investigator), or death from any cause on study. Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or progression of non-target lesions. Death on study was defined as death from any cause within 30 days of the last dose of study treatment regimen. Kaplan-Meier estimates were used for evaluation.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Baseline up to end of study (up to approximately 7.5 years) OS was defined as the time from the date of randomization to the date of death from any cause. Kaplan-Meier estimates were used for evaluation.
Objective Response Rate (ORR) Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, up to end of study (up to approximately 7.5 years) Objective Response Rate was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR) based on the investigator assessment using RECIST v 1.1. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Duration of Objective Tumor Response Screening, at the end of Cycle 4 (cycle = 14 days) and every fourth cycle thereafter until disease progression or death, whichever occurred first, up to end of study (up to approximately 7.5 years) Duration of objective tumor response in participants with measurable soft tissue disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST Version 1.1. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or progression of non-target lesions.
Number of Participants With Adverse Events (AEs) Baseline until end of study (up to approximately 7.5 years) An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Death on study was defined as death from any cause within 30 days of the last dose of study treatment regimen.
Serum Concentration of Ipatasertib Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose
Trial Locations
- Locations (34)
Univ of Calif, Los Angeles; Hematology/Oncology
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital;Oncology
🇺🇸Boston, Massachusetts, United States
Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
🇮🇹Pisa, Toscana, Italy
Institut Gustave Roussy; Departement Oncologie Medicale
🇫🇷Villejuif, France
St Vincent'S Hospital; Oncology
🇰🇷Suwon, Korea, Republic of
Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
🇩🇪Heidelberg, Germany
Gleneagles Medical Centre
🇲🇾Penang, Malaysia
Mount Vernon Hospital; Centre For Cancer Treatment
🇬🇧Northwood, United Kingdom
Asan Medical Center; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
🇩🇪Berlin, Germany
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
🇪🇸Madrid, Spain
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
🇮🇹Padova, Veneto, Italy
Oncocare Cancer Centre
🇸🇬Singapore, Singapore
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Royal Marsden Hospital; Dept of Med-Onc
🇬🇧London, United Kingdom
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Hospital Universiti Sains Malaysia [Neurology]
🇲🇾Kubang Kerian, Kelantan, Malaysia
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
🇮🇹Genova, Liguria, Italy
University Malaya Medical Centre; Clinical Oncology Unit,
🇲🇾Kuala Lumpur, Malaysia
Gachon Medical School Gil Medical Centre; Internal Medicine
🇰🇷Incheon, Korea, Republic of
Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
🇩🇪Hannover, Germany
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hosp; Dept Internal Med Hem Onc
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Cancer Centre; Medical Oncology
🇸🇬Singapore, Singapore
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
National Taiwan Uni Hospital; Dept of Oncology
🇨🇳Taipei, Taiwan
National Cheng Kung Univ Hosp
🇨🇳Tainan, Taiwan
Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
🇨🇳Taoyuan, Taiwan
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Queen Mary Hospital; Dept. of Clinical Oncology
ðŸ‡ðŸ‡°Hong Kong, Hong Kong