Overview

This trial is active, not recruiting.

Condition gastric cancer
Treatments 5-fluorouracil, gdc-0068, leucovorin, oxaliplatin, placebo
Phase phase 2
Target AKT
Sponsor Genentech, Inc.
Start date August 2013
End date June 2015
Trial size 153 participants
Trial identifier NCT01896531, 2012-002080-10, GO28341

Summary

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy of GDC-0068 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 GDC-0068 or placebo orally daily on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6 on Day 1 of each cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs (up to approximately 2 years).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double-blind
Primary purpose treatment
Arm
(Experimental)
Participants will receive oral GDC-0068 on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
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.
gdc-0068
Participants will receive GDC-0068, 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 Comparator)
Participants will receive the placebo equivalent to GDC-0068 on Days 1 to 7 of each 14-day cycle in combination with mFOLFOX6, administered on Day 1 of each cycle.
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.
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.

Primary Outcomes

Measure
Progression-free Survival (PFS) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in All Participants
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)
PFS as Determined by Investigator According to RECIST v1.1 in Participants who Have Phosphatase and Tensin Homolog (PTEN) Loss Tumors or who are Akt Diagnostic-positive (Akt Dx+)
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)

Secondary Outcomes

Measure
Overall Survival Duration (All Participants)
time frame: Baseline until death (up to approximately 2 years)
Overall Survival Duration (in Participants Who Have PTEN Loss Tumors or who are Akt Dx+)
time frame: Baseline until death (up to approximately 2 years)
Percentage of participants with objective tumor response as Determined by Investigator According to RECIST v1.1 (All Participants)
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)
Percentage of participants with objective tumor response as Determined by Investigator According to RECIST v1.1 (in Participants Who Have PTEN Loss Tumors or who are Akt Dx+)
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)
Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1 (All Participants)
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)
Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1 (in Participants Who Have PTEN Loss Tumors or who are Akt Dx+)
time frame: Baseline until disease progression, intolerable toxicity, elective withdrawal from the study, death, or study completion or termination, whichever occurs first (assessed up to 2 years)
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline up to approximately 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Randomized, Phase II, Placebo-Controlled Study of GDC-0068, an Inhibitor to Akt, in Combination With Fluoropyrimidine Plus Oxaliplatin in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Genentech, Inc..