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

NCT ID: NCT01896531

Last Updated: 2022-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-14
• Study Completion Date: 2021-01-26

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ipatasertib + mFOLFOX6

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.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: 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

Intervention Type: 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.

Leucovorin

Intervention Type: 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.

Oxaliplatin

Intervention Type: 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

Placebo + mFOLFOX6

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.

Group Type: PLACEBO_COMPARATOR

5-Fluorouracil

Intervention Type: 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.

Leucovorin

Intervention Type: 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.

Oxaliplatin

Intervention Type: 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

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Univ of Calif, Los Angeles; Hematology/Oncology

Los Angeles, California, United States

Massachusetts General Hospital;Oncology

Boston, Massachusetts, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

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

Berlin, , Germany

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

Hanover, , Germany

Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen

Heidelberg, , Germany

Queen Mary Hospital; Dept. of Clinical Oncology

Hong Kong, , Hong Kong

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

Genoa, Liguria, Italy

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

Pisa, Tuscany, Italy

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda

Padua, Veneto, Italy

Hospital Universiti Sains Malaysia [Neurology]

Kubang Kerian, Kelantan, Malaysia

Gleneagles Medical Centre

George Town, , Malaysia

University Malaya Medical Centre; Clinical Oncology Unit,

Kuala Lumpur, , Malaysia

National Cancer Centre; Medical Oncology

Singapore, , Singapore

Oncocare Cancer Centre

Singapore, , Singapore

Kyungpook National University Hospital

Daegu, , South Korea

Gachon Medical School Gil Medical Centre; Internal Medicine

Incheon, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Asan Medical Center; Medical Oncology

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hosp; Dept Internal Med Hem Onc

Seoul, , South Korea

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

Seoul, , South Korea

St Vincent'S Hospital; Oncology

Suwon, , South Korea

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, , Spain

National Cheng Kung Univ Hosp

Tainan City, , Taiwan

National Taiwan Uni Hospital; Dept of Oncology

Taipei, , Taiwan

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

Taoyuan District, , Taiwan

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 Kingdom

Countries

United States; France; Germany; Hong Kong; Italy; Malaysia; Singapore; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30592991 (View on PubMed)

Other Identifiers

2012-002080-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28341

Identifier Type: -

Identifier Source: org_study_id