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

Breast Cancer Clinical Trial

— FINER  

Official title:

Double-Blind Placebo-Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib as Treatment for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04650581
• Other study ID #: MA40
• Secondary ID: 2101M041883
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 27, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Ipatasertib
400 mg PO QD days 1-21 every 28 days
• Fulvestrant
500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

Other:
• Placebo
PO QD days 1-21 every 28 days

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Southern Highlands Cancer Centre	Bowral	New South Wales
Australia	St John of God Bunbury	Bunbury	Western Australia
Australia	Victorian Breast and Oncology Care	East Melbourne	Victoria
Australia	The Northern Hospital	Epping	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Canberra Hospital	Garran
Australia	Lake Macquarie Private Hospital	Gateshead	New South Wales
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Royal Brisbane and Womens Hospital	Herston
Australia	Macquarie University Hospital	Macquarie University	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Shoalhaven Cancer Care Centre	Nowra	New South Wales
Australia	Sunshine Hospital	St. Albans	Victoria
Australia	Toowoomba Hospital	Toowoomba	Queensland
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	William Osler Health System	Brampton	Ontario
Canada	Centre Integre de Sante et de Services Sociaux	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM-Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Regional Health Authority B, Zone 2	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Sciences Centre/	Thunder Bay	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
New Zealand	Auckland City Hospital	Auckland
New Zealand	Wellington Cancer Centre, Wellington Hospital	Wellington

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) using RECIST 1.1		5 years
Secondary	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
Secondary	Investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN non-altered cohort		5 years
Secondary	PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts		5 years
Secondary	Response rate (RR) (per RECIST 1.1)		5 years
Secondary	Duration of Response (DoR)		5 years
Secondary	Clinical Benefit Rate (CBR);		5 years
Secondary	Overall survival (OS)		5 years
Secondary	Time to commencement of subsequent line of systemic therapy or death (TSST)		5 years
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0		5 years
Secondary	Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire		5 years
Secondary	Adverse events as measured using NCI PRO-CTCAE questionnaire		5 years
Secondary	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
Secondary	Economic Evaluation of health utilities measured using EQ-5D-5L		5 years