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 (FINER)

• ClinicalTrials.gov Identifier: NCT04650581
• Recruitment Status: Active, not recruiting
• First Posted: December 2, 2020
• Last Update Posted: May 9, 2024
• Sponsor: Canadian Cancer Trials Group
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: November 24, 2020
• First Posted Date: December 2, 2020
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: January 27, 2021
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 1, 2020): Progression-free survival (PFS) using RECIST 1.1 [ Time Frame: 5 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 1, 2020)

• To compare the two treatment arms with respect to investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN altered cohort [ Time Frame: 5 years ]
• Investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN non-altered cohort [ Time Frame: 5 years ]
• PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts [ Time Frame: 5 years ]
• Response rate (RR) (per RECIST 1.1) [ Time Frame: 5 years ]
• Duration of Response (DoR) [ Time Frame: 5 years ]
• Clinical Benefit Rate (CBR); [ Time Frame: 5 years ]
• Overall survival (OS) [ Time Frame: 5 years ]
• Time to commencement of subsequent line of systemic therapy or death (TSST) [ Time Frame: 5 years ]
• Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 [ Time Frame: 5 years ]
• Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire [ Time Frame: 5 years ]
• Adverse events as measured using NCI PRO-CTCAE questionnaire [ Time Frame: 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. [ Time Frame: 5 years ]
• Economic Evaluation of health utilities measured using EQ-5D-5L [ Time Frame: 5 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Ipatasertib
  400 mg PO QD days 1-21 every 28 days
• Drug: 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

Study Arms

• Experimental: Ipatasertib + Fulvestrant
  Interventions:

  • Drug: Ipatasertib
  • Drug: Fulvestrant
• Placebo Comparator: Placebo
  Interventions:

  • Drug: Fulvestrant
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 1, 2020): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, New Zealand

Administrative Information

• NCT Number: NCT04650581
• Other Study ID Numbers: MA40; 2101 ( Other Identifier: BCT ); M041883 ( Other Identifier: Hoffmann-LaRoche Ltd. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche

Investigators

• Study Chair: Stephen Chia; BCCA - Vancouver Cancer Centre, BC Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: May 2024