A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: 5-Fluorouracil; Ipatasertib; Leucovorin; Oxaliplatin; Placebo
Intervention description: 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.; 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.; 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.; 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; 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 MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Ipatasertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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