FINER: 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

Sponsor
Canadian Cancer Trials Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04650581
Collaborator
Hoffmann-La Roche (Industry)
250
38
2
73
6.6
0.1

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 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
Actual Study Start Date :
Dec 1, 2020
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ipatasertib + Fulvestrant

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

Placebo Comparator: Placebo

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

Outcome Measures

Primary Outcome Measures

  1. Progression-free survival (PFS) using RECIST 1.1 [5 years]

Secondary Outcome Measures

  1. 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]

  2. Investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN non-altered cohort [5 years]

  3. PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts [5 years]

  4. Response rate (RR) (per RECIST 1.1) [5 years]

  5. Duration of Response (DoR) [5 years]

  6. Clinical Benefit Rate (CBR); [5 years]

  7. Overall survival (OS) [5 years]

  8. Time to commencement of subsequent line of systemic therapy or death (TSST) [5 years]

  9. Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 [5 years]

  10. Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire [5 years]

  11. Adverse events as measured using NCI PRO-CTCAE questionnaire [5 years]

  12. 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]

  13. Economic Evaluation of health utilities measured using EQ-5D-5L [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Southern Highlands Cancer Centre Bowral New South Wales Australia 2576
2 Lake Macquarie Private Hospital Gateshead New South Wales Australia 2324
3 Gosford Hospital Gosford New South Wales Australia 2250
4 Macquarie University Hospital Macquarie University New South Wales Australia 2109
5 Shoalhaven Cancer Care Centre Nowra New South Wales Australia 2541
6 Prince of Wales Hospital Randwick New South Wales Australia 2031
7 Sunshine Coast University Hospital Birtinya Queensland Australia 4575
8 Toowoomba Hospital Toowoomba Queensland Australia 4350
9 Victorian Breast and Oncology Care East Melbourne Victoria Australia 3002
10 Frankston Hospital Frankston Victoria Australia 3199
11 Alfred Hospital Melbourne Victoria Australia 3004
12 Sunshine Hospital St. Albans Victoria Australia 3021
13 St John of God Bunbury Bunbury Western Australia Australia 6230
14 Fiona Stanley Hospital Murdoch Western Australia Australia 6150
15 Royal Brisbane and Womens Hospital Herston Australia 4029
16 BCCA - Cancer Centre for the Southern Interior Kelowna British Columbia Canada V1Y 5L3
17 BCCA - Fraser Valley Cancer Centre Surrey British Columbia Canada V3V 1Z2
18 BCCA - Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
19 The Moncton Hospital Moncton New Brunswick Canada E1C 6Z8
20 Regional Health Authority B, Zone 2 Saint John New Brunswick Canada E2L 4L2
21 QEII Health Sciences Centre Halifax Nova Scotia Canada B3H 1V7
22 Royal Victoria Regional Health Centre Barrie Ontario Canada L4M 6M2
23 William Osler Health System Brampton Ontario Canada L6R 3J7
24 Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
25 Kingston Health Sciences Centre Kingston Ontario Canada K7L 2V7
26 London Regional Cancer Program London Ontario Canada N6A 5W9
27 Stronach Regional Health Centre at Southlake Newmarket Ontario Canada L3Y 2P9
28 Ottawa Hospital Research Institute Ottawa Ontario Canada K1H 8L6
29 Algoma District Cancer Program Sault Ste. Marie Ontario Canada P6B 0A8
30 Thunder Bay Regional Health Sciences Centre/ Thunder Bay Ontario Canada P7B 6V4
31 University Health Network Toronto Ontario Canada M5G 2M9
32 Windsor Regional Cancer Centre Windsor Ontario Canada N8W 2X3
33 Centre Integre de Sante et de Services Sociaux Greenfield Park Quebec Canada J4V 2H1
34 CHUM-Centre Hospitalier de l'Universite de Montreal Montreal Quebec Canada H2X 3E4
35 CHA-Hopital Du St-Sacrement Quebec City Quebec Canada G1S 4L8
36 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1
37 Saskatoon Cancer Centre Saskatoon Saskatchewan Canada S7N 4H4
38 Wellington Cancer Centre, Wellington Hospital Wellington New Zealand 2

Sponsors and Collaborators

  • Canadian Cancer Trials Group
  • Hoffmann-La Roche

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Canadian Cancer Trials Group
ClinicalTrials.gov Identifier:
NCT04650581
Other Study ID Numbers:
  • MA40
  • 2101
  • M041883
First Posted:
Dec 2, 2020
Last Update Posted:
Aug 9, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 9, 2022