A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01896531
• Other study ID #: GO28341
• Secondary ID: 2012-002080-10
• Status: Completed
• Phase: Phase 2
• Start date: August 14, 2013
• Est. completion date: January 26, 2021

Study information

• Verified date: February 2022
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: January 26, 2021
• Est. primary completion date: June 3, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• 5-Fluorouracil
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.
• Ipatasertib
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.
• Leucovorin
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.
• Oxaliplatin
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
• Placebo
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.

Locations

Country	Name	City	State
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Germany	Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.	Berlin
Germany	Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover
Germany	Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen	Heidelberg
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica	Pisa	Toscana
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Gachon Medical School Gil Medical Centre; Internal Medicine	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center; Medical Oncology	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hosp; Dept Internal Med Hem Onc	Seoul
Korea, Republic of	Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.	Seoul
Korea, Republic of	St Vincent'S Hospital; Oncology	Suwon
Malaysia	University Malaya Medical Centre; Clinical Oncology Unit,	Kuala Lumpur
Malaysia	Hospital Universiti Sains Malaysia [Neurology]	Kubang Kerian	Kelantan
Malaysia	Gleneagles Medical Centre	Penang
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	Oncocare Cancer Centre	Singapore
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood
United Kingdom	The Royal Marsden Hospital	Sutton
United States	Massachusetts General Hospital;Oncology	Boston	Massachusetts
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Univ of Calif, Los Angeles; Hematology/Oncology	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Malaysia,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	Baseline up to end of study (up to approximately 7.5 years)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	Baseline until end of study (up to approximately 7.5 years)
Secondary	Serum Concentration of Ipatasertib		Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose