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 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CO410122019-001072-11
• Study Type: interventional
• Target: 20
• Locations: 8 countries
• Sites: 20

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Phase III: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

  PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of ≥ 5 millimeters (mm).

  From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months

Secondary Outcomes (13)

• Phase Ib: Number of Participants With Adverse Events and Adverse Events With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

  Up to 36 Months

• Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720

  Cycle 1, Day 1 and 15: 0.25 hours pre-dose, 0.5, 1, 2, 3, 4 and 6 hours post- dose ; Cycle 2, Day 15: 0.25 hours pre-dose; Cycle 3, Day 15: 0.15 hours pre-dose, 2 hours post-dose (each cycle = 28 days)

• Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma

  Cycle 1: Day 1 and Day 15

• Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720

  Cycle 1: Day 1 and Day 15

• Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720

  Cycle 1: Day 1 and Day 15

Study Arms (2)

Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant

EXPERIMENTAL

Drug: Ipatasertib; Drug: Palbociclib; Drug: Fulvestrant

Phase 3: Placebo + Palbociclib + Fulvestrant

PLACEBO COMPARATOR

Drug: Placebo; Drug: Palbociclib; Drug: Fulvestrant

Interventions

Ipatasertib DRUG

Phase 1b: Ipatasertib, 300 mg starting dose administered orally once daily (PO QD) during an initial 5-7 day run-in period, then continued on Days 1-21 during the first cycle. Starting with Cycle 2, Day 1 ipatasertib will be taken orally once daily on Days 1-21 of each 28-day cycle. Phase 3: Ipatasertib, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.

Also known as: RO5532961, GDC-0068

Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant

Placebo DRUG

Phase 3: Matching placebo, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.

Phase 3: Placebo + Palbociclib + Fulvestrant

Palbociclib DRUG

Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.

Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant; Phase 3: Placebo + Palbociclib + Fulvestrant

Fulvestrant DRUG

Fulvestrant, 500 mg administered as two intramuscular injections of 250 mg each on Cycle 1 Days 1 and 15 and Day 1 of each subsequent 28-day cycle.

Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant; Phase 3: Placebo + Palbociclib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 contraceptive methods, 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

You may not qualify if:

• 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 III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (20)

Piedmont Cancer Institute, PC

Atlanta, Georgia, 30318, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114-2621, United States

Location

Dana-Farber Cancer Institute; GYN Oncology

Boston, Massachusetts, 02215, United States

Location

Summit Medical Group; MD Anderson Cancer Center

Florham Park, New Jersey, 07932, United States

Location

Cabrini Medical Centre; Oncology

Malvern, Victoria, 3144, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Tom Baker Cancer Centre-Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Juravinski Cancer Clinic; Clinical Trials Department

Hamilton, Ontario, L8V 5C2, Canada

Location

Hopital du Saint Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Clínico Universitario de Valencia; Servicio de Oncología

Valencia, 46010, Spain

Location

The Royal Marsden Hospital; Dept of Medicine

London, SW3 5PT, United Kingdom

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ipatasertib; palbociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The study was terminated before initiation of Phase III as per sponsor's decision; hence no primary efficacy and secondary efficacy, safety and pharmacokinetic outcome measures were assessed or analyzed, and no data was collected for Phase III.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 19, 2019
• Study Start: November 21, 2019
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: November 8, 2024
• Results First Posted: November 8, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); KR (1); CA (3); US (5); JP (2); BR (2); ES (2); GB (3)