Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

NCT ID: NCT04650581

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-27
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).

Detailed Description

Patients enrolled in this study will receive either Ipatasertib plus Fulvestrant or placebo (a substance that looks like the study drug but does not have any active or medicinal ingredient) plus Fulvestant. The study will provide information about the ability of Ipatasertib plus Fulvestrant to control the cancer, the side effects and safety of the treatment, how patients feel while taking the treatment and associated costs.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Fulvestrant

Intervention Type: DRUG

500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

Placebo

Intervention Type: OTHER

PO QD days 1-21 every 28 days

Ipatasertib + Fulvestrant

Group Type: EXPERIMENTAL

Ipatasertib

Intervention Type: DRUG

400 mg PO QD days 1-21 every 28 days

Fulvestrant

Intervention Type: DRUG

500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

Interventions

Ipatasertib

400 mg PO QD days 1-21 every 28 days

Intervention Type: DRUG

Fulvestrant

500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

Intervention Type: DRUG

Placebo

PO QD days 1-21 every 28 days

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
• Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
• Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease
• Evidence of clinically and/or radiologically documented disease
• ≥ 18 years of age
• ECOG performance status of 0 or 1
• No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy

• Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting.
• Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study
• Adequate hematology and organ function, in the absence of growth factors

• Absolute neutrophils > 1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L
• Hemoglobin > 90 g/L
• Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
• ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)
• Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis)
• Fasting glucose ≤ 8.3 mmol/L
• HbA1c ≤ 7.5%
• Serum albumin ≥ 30 g/L
• INR ≤ 1.2
• Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation

Exclusion Criteria

• Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days
• Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption
• Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors
• Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome
• Active or uncontrolled infections or serious illnesses or medical conditions
• Clinically significant liver diseases
• History of lung disease or history of opportunistic infections
• Type 1 or Type 2 diabetes mellitus requiring insulin
• Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia
• Known abnormalities in coagulation
• History of hypersensitivity to the study drugs or components
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Chia

Role: STUDY_CHAIR

BCCA - Vancouver Cancer Centre, BC Canada

Locations

Southern Highlands Cancer Centre

Bowral, New South Wales, Australia

Lake Macquarie Private Hospital

Gateshead, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Macquarie University Hospital

Macquarie University, New South Wales, Australia

Shoalhaven Cancer Care Centre

Nowra, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Victorian Breast and Oncology Care

East Melbourne, Victoria, Australia

The Northern Hospital

Epping, Victoria, Australia

Frankston Hospital

Frankston, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Sunshine Hospital

St Albans, Victoria, Australia

St John of God Bunbury

Bunbury, Western Australia, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Canberra Hospital

Garran, , Australia

Royal Brisbane and Womens Hospital

Herston, , Australia

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Regional Health Authority B, Zone 2

Saint John, New Brunswick, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

William Osler Health System

Brampton, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Thunder Bay Regional Health Sciences Centre/

Thunder Bay, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Centre Integre de Sante et de Services Sociaux

Greenfield Park, Quebec, Canada

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Auckland City Hospital

Auckland, , New Zealand

Wellington Cancer Centre, Wellington Hospital

Wellington, , New Zealand

Countries

Australia; Canada; New Zealand

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2101

Identifier Type: OTHER

Identifier Source: secondary_id

M041883

Identifier Type: OTHER

Identifier Source: secondary_id

MA40

Identifier Type: -

Identifier Source: org_study_id