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
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT04650581
- Lead Sponsor
- Canadian Cancer Trials Group
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 250
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ipatasertib + Fulvestrant Fulvestrant - Placebo Placebo - Placebo Fulvestrant - Ipatasertib + Fulvestrant Ipatasertib -
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) using RECIST 1.1 5 years
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR); 5 years To compare the two treatment arms with respect to investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN altered cohort 5 years Investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN non-altered cohort 5 years Response rate (RR) (per RECIST 1.1) 5 years Economic Evaluation of health utilities measured using EQ-5D-5L 5 years Overall survival (OS) 5 years Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire 5 years Duration of Response (DoR) 5 years Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 5 years Adverse events as measured using NCI PRO-CTCAE questionnaire 5 years Time to commencement of subsequent line of systemic therapy or death (TSST) 5 years PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts 5 years Economic Evaluation of healthcare utilization using average cost per study subject by treatment arm to estimate an overall mean cost per study arm. 5 years
Trial Locations
- Locations (39)
QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, 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
🇨🇦Quebec City, Quebec, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Victorian Breast and Oncology Care
🇦🇺East Melbourne, Victoria, Australia
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Algoma District Cancer Program
🇨🇦Sault Ste. Marie, Ontario, Canada
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Southern Highlands Cancer Centre
🇦🇺Bowral, New South Wales, Australia
Lake Macquarie Private Hospital
🇦🇺Gateshead, New South Wales, Australia
Macquarie University Hospital
🇦🇺Macquarie University, New South Wales, Australia
Toowoomba Hospital
🇦🇺Toowoomba, Queensland, Australia
Shoalhaven Cancer Care Centre
🇦🇺Nowra, New South Wales, Australia
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
The Northern Hospital
🇦🇺Epping, Victoria, Australia
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
St John of God Bunbury
🇦🇺Bunbury, Western Australia, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Canberra Hospital
🇦🇺Garran, Australia
Sunshine Hospital
🇦🇺St. Albans, Victoria, Australia
Royal Brisbane and Womens Hospital
🇦🇺Herston, Australia
BCCA - Fraser Valley Cancer Centre
🇨🇦Surrey, British Columbia, Canada
BCCA - Cancer Centre for the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
BCCA - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Regional Health Authority B, Zone 2
🇨🇦Saint John, New Brunswick, Canada
William Osler Health System
🇨🇦Brampton, Ontario, Canada
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Stronach Regional Health Centre at Southlake
🇨🇦Newmarket, Ontario, Canada
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
London Regional Cancer Program
🇨🇦London, 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
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Auckland City Hospital
🇳🇿Auckland, New Zealand
Wellington Cancer Centre, Wellington Hospital
🇳🇿Wellington, New Zealand