Clinical trial NCT01896531: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-Free Survival (PFS) in All Randomized Participants and Participants With PTEN Loss Tumors at Primary Analysis
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: Baseline up to end of study (up to approximately 7.5 years)
measure: Objective Response Rate (ORR)
timeFrame: 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)
measure: Duration of Objective Tumor Response
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline until end of study (up to approximately 7.5 years)
measure: Serum Concentration of Ipatasertib
timeFrame: Day 1 at 1 hour and 4 hours post-dose; Day 5, pre-dose and 2 hours post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univ of Calif, Los Angeles; Hematology/Oncology
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital;Oncology
state: Massachusetts
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
city: Berlin
country: Germany
facility: Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
city: Heidelberg
country: Germany
facility: Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Dept. of Clinical Oncology
city: Genova
country: Italy
facility: IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
state: Liguria
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
state: Veneto
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon Medical School Gil Medical Centre; Internal Medicine
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hosp; Dept Internal Med Hem Onc
city: Seoul
country: Korea, Republic of
facility: Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
city: Suwon
country: Korea, Republic of
facility: St Vincent'S Hospital; Oncology
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia [Neurology]
state: Kelantan
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre; Clinical Oncology Unit,
city: Penang
country: Malaysia
facility: Gleneagles Medical Centre
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: Singapore
country: Singapore
facility: Oncocare Cancer Centre
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Dept of Oncology
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Med-Onc
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital; Centre For Cancer Treatment
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.