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

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ClinicalTrials.gov Identifier: NCT01896531
Recruitment Status : Active, not recruiting
First Posted : July 11, 2013
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief 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).

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: 5-Fluorouracil Drug: GDC-0068 Drug: Leucovorin Drug: Oxaliplatin Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 31, 2013
Actual Primary Completion Date : June 30, 2015
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arm Intervention/treatment
Experimental: GDC-0068 + mFOLFOX6
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.
Drug: 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.

Drug: 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.

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.

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

Placebo Comparator: Placebo + mFOLFOX6
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.
Drug: 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.

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.

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

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.




Primary Outcome Measures :
  1. 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) ]
  2. 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 Outcome Measures :
  1. Overall Survival Duration (All Participants) [ Time Frame: Baseline until death (up to approximately 2 years) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 2 years ]

Other Outcome Measures:
  1. Minimum Observed Serum Trough Concentration (Cmin) of GDC-0068 [ Time Frame: 0 to 2 hours pre-dose on Day 7 of Cycle 1 (Cycle length=14 days) ]
  2. Area under the Concentration-Time Curve From Time Zero to 24 hours (AUC0-24) of GDC-0068 [ Time Frame: 0.5 to 2 hours and 4 to 6 hours post-dose on Day 1 of Cycle 1; 0 to 2 hours pre-dose and 2 to 5 hours post-dose on Day 7 of Cycle 1 (Cycle length=14 days) ]
  3. Apparent Oral Clearance (CL/F) of GDC-0068 [ Time Frame: 0.5 to 2 hours and 4 to 6 hours post-dose on Day 1 of Cycle 1; 0 to 2 hours pre-dose and 2 to 5 hours post-dose on Day 7 of Cycle 1 (Cycle length=14 days) ]
  4. Percentage of Participants With European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC QLQ-C30) Score [ Time Frame: Day 1 of Cycles 1 and 2 (Cycle length = 14 days) ]
  5. Percentage of Participants With Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) Score [ Time Frame: Day 1 of Cycles 1 and 2 (Cycle length = 14 days) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01896531


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Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01896531     History of Changes
Other Study ID Numbers: GO28341
2012-002080-10 ( EudraCT Number )
First Posted: July 11, 2013    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs