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

NCT01896531 | Completed Phase 2 Results

• 2 other identifiers: GO283412012-002080-10
• Study Type: interventional
• Target: 153
• Locations: 11 countries
• Sites: 34

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Survival (OS)

  Baseline up to end of study (up to approximately 7.5 years)

• 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)

• 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)

• Number of Participants With Adverse Events (AEs)

  Baseline until end of study (up to approximately 7.5 years)

• Serum Concentration of Ipatasertib

  Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose

Study Arms (2)

Ipatasertib + mFOLFOX6

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Ipatasertib; Drug: Leucovorin; Drug: Oxaliplatin

Placebo + mFOLFOX6

PLACEBO COMPARATOR

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.

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Placebo

Interventions

5-Fluorouracil DRUG

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 + mFOLFOX6; Placebo + mFOLFOX6

Ipatasertib DRUG

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.

Ipatasertib + mFOLFOX6

Leucovorin DRUG

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.

Ipatasertib + mFOLFOX6; Placebo + mFOLFOX6

Oxaliplatin DRUG

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

Ipatasertib + mFOLFOX6; Placebo + mFOLFOX6

Placebo DRUG

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.

Placebo + mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (34)

Univ of Calif, Los Angeles; Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital;Oncology

Boston, Massachusetts, 02114, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.

Berlin, 10117, Germany

Location

Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hanover, 30625, Germany

Location

Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

Location

Queen Mary Hospital; Dept. of Clinical Oncology

Hong Kong, Hong Kong

Location

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genoa, Liguria, 16132, Italy

Location

Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica

Pisa, Tuscany, 56126, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda

Padua, Veneto, 35128, Italy

Location

Hospital Universiti Sains Malaysia [Neurology]

Kubang Kerian, Kelantan, 16150, Malaysia

Location

Gleneagles Medical Centre

George Town, 10050, Malaysia

Location

University Malaya Medical Centre; Clinical Oncology Unit,

Kuala Lumpur, 59100, Malaysia

Location

National Cancer Centre; Medical Oncology

Singapore, 169610, Singapore

Location

Oncocare Cancer Centre

Singapore, 258499, Singapore

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Gachon Medical School Gil Medical Centre; Internal Medicine

Incheon, 405-760, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Asan Medical Center; Medical Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul National University Hosp; Dept Internal Med Hem Onc

Seoul, 110-744, South Korea

Location

Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.

Seoul, 120-752, South Korea

Location

St Vincent'S Hospital; Oncology

Suwon, South Korea

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

National Cheng Kung Univ Hosp

Tainan, 00704, Taiwan

Location

National Taiwan Uni Hospital; Dept of Oncology

Taipei, 100, Taiwan

Location

Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology

Taoyuan District, 333, Taiwan

Location

Royal Marsden Hospital; Dept of Med-Onc

London, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Mount Vernon Hospital; Centre For Cancer Treatment

Northwood, HA6 2RN, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30592991 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Fluorouracil; ipatasertib; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: August 14, 2013
• Primary Completion: June 3, 2015
• Study Completion: January 26, 2021
• Last Updated: March 2, 2022
• Results First Posted: February 17, 2022

Record last verified: 2022-02

Locations

MY (3); SG (2); KR (8); DE (3); IT (3); US (3); ES (3); HK (1); TW (3); FR (1); GB (4)