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A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer

NCT04060862

Description:

The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
  • Official Title: A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CO41012
  • SECONDARY ID: 2019-001072-11
  • NCT ID: NCT04060862

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
IpatasertibRO5532961, GDC-0068Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
PlaceboPhase 3: Placebo + Palbociclib + Fulvestrant
PalbociclibPhase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
FulvestrantPhase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant

Purpose

The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b and Phase 3: Ipatasertib + Palbociclib +FulvestrantExperimental
  • Ipatasertib
  • Palbociclib
  • Fulvestrant
Phase 3: Placebo + Palbociclib + FulvestrantPlacebo Comparator
  • Placebo
  • Palbociclib
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or
             metastatic

          -  For women of childbearing potential: agreement to remain abstinent or use
             contraception, and agreement to refrain from donating eggs

          -  For men: agreement to remain abstinent or use a condom, and agreement to refrain from
             donating sperm

          -  Radiologic/objective relapse during adjuvant endocrine therapy or disease progression
             during the initial 12 months of 1L endocrine therapy in locally advanced unresectable
             or metastatic breast cancer

          -  At least one measurable lesion via Response Evaluation Criteria in Solid Tumors,
             Version 1.1

          -  Phase III only: Tumor specimen from the most recently collected, available tumor
             tissue

        Exclusion Criteria:

          -  Pregnant or breastfeeding, or intending to become pregnant

          -  Prior treatment with fulvestrant or other selective estrogen receptor down-regulator

          -  Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor

          -  Phase Ib only: Prior treatment with CDK4/6 inhibitor

          -  Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer

          -  History of Type I or Type II diabetes mellitus requiring insulin

          -  History of or active inflammatory bowel disease or active bowel inflammation

          -  Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis,
             cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic
             infections
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) in Intent-to-Treat (ITT), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame:From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame:From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Safety Issue:
Description:
Measure:Duration of Objective Response (DOR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame:From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Safety Issue:
Description:
Measure:Clinical Benefit Rate (CBR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame:From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Safety Issue:
Description:
Measure:Overall Survival (OS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1
Time Frame:From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Safety Issue:
Description:
Measure:Time to Deterioration (TTD) in Pain, according to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale
Time Frame:From randomization in Phase 3 to the first documentation of a 10-point or more increase in pain scale from baseline, up to approximately 64 months
Safety Issue:
Description:
Measure:Time to deterioration (TTD) in physical functioning (PF)
Time Frame:From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the PF scale of the EORTC QLQ-C30, up to approx 64 months
Safety Issue:
Description:
Measure:TTD in Role Functioning (RF)
Time Frame:From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the RF scale of the EORTC QLQ-C30, up to approx 64 months
Safety Issue:
Description:
Measure:TTD in Global Health Survey (GHS)/Health-Related Quality of Life (HRQoL)
Time Frame:From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the GHS/HRQoL scale of the EORTC QLQ-C30, up to approx 64 months
Safety Issue:
Description:
Measure:Number of Participants with Adverse Events
Time Frame:From baseline to end of study, up to approximately 64 months
Safety Issue:
Description:
Measure:Phase 1b: Plasma Concentration of Ipatasertib and its Metabolite, G-037720 and Palbociclib
Time Frame:Ipatasertib & G-037720: predose, postdose at 0.5,1,3,4,6hr of Cycle(C) 1, Day(D) 1 & C1D15, predose on C2D15 & C3D15 & 2hr post-dose on C3D15; Palbociclib: predose on C2D15 & C3D15
Safety Issue:
Description:
Measure:Phase 3: Plasma Concentration of Ipatasertib or its Placebo and its Metabolite, G-037720
Time Frame:1-3 hrs after ipatasertib or its placebo on C1D1 and C1D15, Predose on C1D15, C2D15 and 2-4 hrs after ipatasertib or its placebo on C2D15
Safety Issue:
Description:

Details

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

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