Back to resultsA Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
Primary Purpose
Gastric Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
5-Fluorouracil
Ipatasertib
Leucovorin
Oxaliplatin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Univ of Calif, Los Angeles; Hematology/Oncology
- Massachusetts General Hospital;Oncology
- University of Texas M.D. Anderson Cancer Center
- Institut Gustave Roussy; Departement Oncologie Medicale
- Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
- Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
- Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
- Queen Mary Hospital; Dept. of Clinical Oncology
- IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
- Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
- IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
- Kyungpook National University Hospital
- Gachon Medical School Gil Medical Centre; Internal Medicine
- Seoul National University Bundang Hospital
- Asan Medical Center; Medical Oncology
- Samsung Medical Center
- Seoul National University Hosp; Dept Internal Med Hem Onc
- Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
- St Vincent'S Hospital; Oncology
- Hospital Universiti Sains Malaysia [Neurology]
- University Malaya Medical Centre; Clinical Oncology Unit,
- Gleneagles Medical Centre
- National Cancer Centre; Medical Oncology
- Oncocare Cancer Centre
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
- Hospital Clinico Universitario de Valencia
- National Cheng Kung Univ Hosp
- National Taiwan Uni Hospital; Dept of Oncology
- Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
- Royal Marsden Hospital; Dept of Med-Onc
- Sarah Cannon Research Institute
- Mount Vernon Hospital; Centre For Cancer Treatment
- The Royal Marsden Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ipatasertib + mFOLFOX6
Placebo + mFOLFOX6
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis
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
Overall Survival (OS)
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)
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
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)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01896531
Brief Title
A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
Official Title
A Randomized, Phase II, Placebo-controlled Study of Ipatasertib (GDC-0068), an Inhibitor to Akt, in Combination With Fluoropyrimidine Plus Oxaliplatin in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
August 14, 2013 (Actual)
Primary Completion Date
June 3, 2015 (Actual)
Study Completion Date
January 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
153 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ipatasertib + mFOLFOX6
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + mFOLFOX6
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
Participants will receive bolus and infusional 5-fluorouracil on Day 1 of each 14-day cycle (as a part of mFOLFOX6 therapy), until disease progression or unacceptable toxicity. The infusion times for infusional 5-fluorouracil may be determined per local and/or institutional standards and product labeling.
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Intervention Description
Participants will receive ipatasertib, 600 milligrams (mg) orally once daily on Days 1 to 7 of each 14-day cycle until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Participants will receive leucovorin or equivalent substitute orally, on Day 1 of each 14-day cycle (as a part of mFOLFOX6 therapy), until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Participants will receive oxaliplatin via intravenous (IV) infusion on Day 1 of each 14-day cycle (part of mFOLFOX6 therapy). Oxaliplatin will be discontinued after completion of 8 cycles
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching oral placebo capsules once daily on Days 1 to 7 of each 14-day cycle until disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis
Description
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.
Time Frame
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
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
Baseline up to end of study (up to approximately 7.5 years)
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
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)
Title
Duration of Objective Tumor Response
Description
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.
Time Frame
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)
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Baseline until end of study (up to approximately 7.5 years)
Title
Serum Concentration of Ipatasertib
Time Frame
Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Univ of Calif, Los Angeles; Hematology/Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Massachusetts General Hospital;Oncology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Institut Gustave Roussy; Departement Oncologie Medicale
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Queen Mary Hospital; Dept. of Clinical Oncology
City
Hong Kong
Country
Hong Kong
Facility Name
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Kyungpook National University Hospital
City
Daegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Gachon Medical School Gil Medical Centre; Internal Medicine
City
Incheon
ZIP/Postal Code
405-760
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
ZIP/Postal Code
13605
Country
Korea, Republic of
Facility Name
Asan Medical Center; Medical Oncology
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul National University Hosp; Dept Internal Med Hem Onc
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
St Vincent'S Hospital; Oncology
City
Suwon
Country
Korea, Republic of
Facility Name
Hospital Universiti Sains Malaysia [Neurology]
City
Kubang Kerian
State/Province
Kelantan
ZIP/Postal Code
16150
Country
Malaysia
Facility Name
University Malaya Medical Centre; Clinical Oncology Unit,
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Gleneagles Medical Centre
City
Penang
ZIP/Postal Code
10050
Country
Malaysia
Facility Name
National Cancer Centre; Medical Oncology
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Oncocare Cancer Centre
City
Singapore
ZIP/Postal Code
258499
Country
Singapore
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
National Cheng Kung Univ Hosp
City
Tainan
ZIP/Postal Code
00704
Country
Taiwan
Facility Name
National Taiwan Uni Hospital; Dept of Oncology
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Facility Name
Royal Marsden Hospital; Dept of Med-Onc
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Sarah Cannon Research Institute
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
Mount Vernon Hospital; Centre For Cancer Treatment
City
Northwood
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
The Royal Marsden Hospital
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
30592991
Citation
Bang YJ, Kang YK, Ng M, Chung HC, Wainberg ZA, Gendreau S, Chan WY, Xu N, Maslyar D, Meng R, Chau I, Ajani JA. A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer. Eur J Cancer. 2019 Feb;108:17-24. doi: 10.1016/j.ejca.2018.11.017. Epub 2018 Dec 25.
Results Reference
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A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
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