Clinical Trials /

A Study Evaluating the Efficacy and Safety of GDC-0077 + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer

NCT04191499

Description:

This study will evaluate the efficacy, safety, and pharmacokinetics of GDC-0077 in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of GDC-0077 + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer
  • Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of GDC-0077 Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: WO41554
  • SECONDARY ID: 2019-002455-42
  • NCT ID: NCT04191499

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
GDC-0077GDC-0077 + Palbociclib + Fulvestrant
PlaceboPlacebo + Palbociclib + Fulvestrant
PalbociclibGDC-0077 + Palbociclib + Fulvestrant
FulvestrantGDC-0077 + Palbociclib + Fulvestrant

Purpose

This study will evaluate the efficacy, safety, and pharmacokinetics of GDC-0077 in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Trial Arms

NameTypeDescriptionInterventions
GDC-0077 + Palbociclib + FulvestrantExperimentalParticipants will receive GDC-0077, palbociclib, and fulvestrant.
  • GDC-0077
  • Palbociclib
  • Fulvestrant
Placebo + Palbociclib + FulvestrantPlacebo ComparatorParticipants will receive placebo, palbociclib, and fulvestrant.
  • Placebo
  • Palbociclib
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria

          -  Confirmed diagnosis of HR+/HER2- breast cancer

          -  Metastatic or locally advanced disease not amenable to curative therapy

          -  Progression of disease during adjuvant endocrine treatment or within 12 months of
             completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen

          -  Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if
             pre/peri-menopausal

          -  Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA
             via specified test)

          -  Consent to provide fresh or archival tumor tissue specimen

          -  Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1;
             "bone-only" disease, even if considered measurable, is not eligible

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

          -  Life expectancy of > 6 months

          -  Adequate hematologic and organ function within 14 days prior to initiation of study
             treatment

        Exclusion Criteria

          -  Metaplastic breast cancer

          -  Any history of leptomeningeal disease or carcinomatous meningitis

          -  Any prior systemic therapy for metastatic breast cancer

          -  Prior treatment with fulvestrant or any selective estrogen-receptor degrader

          -  Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of
             action is to inhibit the PI3K-AKT-mTOR pathway

          -  Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or
             any history of Type 1 diabetes

          -  Known and untreated, or active CNS metastases. Patients with a history of treated CNS
             metastases are eligible

          -  Active inflammatory or infectious conditions in either eye, or any eye conditions
             expected to require surgery during the study treatment period

          -  Symptomatic active lung disease, or requiring daily supplemental oxygen

          -  History of inflammatory bowel disease or active bowel inflammation

          -  Anti-cancer therapy within 2 weeks before study entry

          -  Investigational drug(s) within 4 weeks before randomization

          -  Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow
             transplantation

          -  Chronic corticosteroid therapy or immunosuppressants

          -  Pregnant, lactating, or breastfeeding, or intending to become pregnant during the
             study or within 60 days after the final dose of study treatment

          -  Major surgical procedure, or significant traumatic injury, within 28 days prior to Day
             1 of Cycle 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 6 years
Safety Issue:
Description:
Measure:Best Overall Response Rate (BOR)
Time Frame:Up to 6 years
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the first occurrence of a CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Safety Issue:
Description:
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 6 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From randomization to death from any cause (up to 6 years)
Safety Issue:
Description:
Measure:Time to Deterioration (TTD) in Pain
Time Frame:Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Safety Issue:
Description:
Measure:TTD in Physical Function
Time Frame:Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Safety Issue:
Description:
Measure:TTD in Role Function
Time Frame:Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Safety Issue:
Description:
Measure:TTD in Global Health Status
Time Frame:Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events
Time Frame:From randomization through the end of study (up to 6 years)
Safety Issue:
Description:
Measure:Plasma Concentration of GDC-0077
Time Frame:At pre-defined intervals from baseline to the end of study (up to 6 years)
Safety Issue:
Description:
Measure:Plasma Concentration of Palbociclib
Time Frame:At pre-defined intervals from baseline to the end of study (up to 6 years)
Safety Issue:
Description:
Measure:Plasma Concentration of Fulvestrant
Time Frame:At pre-defined intervals from baseline to the end of study (up to 6 years)
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 6, 2019