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
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 |
---|---|---|
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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
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Ipatasertib + Fulvestrant
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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
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Placebo Comparator: Placebo
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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
- Progression-free survival (PFS) using RECIST 1.1 [5 years]
Secondary Outcome Measures
- 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]
- PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts [5 years]
- Response rate (RR) (per RECIST 1.1) [5 years]
- Duration of Response (DoR) [5 years]
- Clinical Benefit Rate (CBR); [5 years]
- Overall survival (OS) [5 years]
- Time to commencement of subsequent line of systemic therapy or death (TSST) [5 years]
- Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 [5 years]
- Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire [5 years]
- Adverse events as measured using NCI PRO-CTCAE questionnaire [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]
- Economic Evaluation of health utilities measured using EQ-5D-5L [5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
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Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
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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
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Evidence of clinically and/or radiologically documented disease
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≥ 18 years of age
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ECOG performance status of 0 or 1
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No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy
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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.
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Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study
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Adequate hematology and organ function, in the absence of growth factors
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Absolute neutrophils > 1.5 x 10^9/L
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Platelets ≥ 100 x 10^9/L
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Hemoglobin > 90 g/L
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Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
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ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)
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Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis)
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Fasting glucose ≤ 8.3 mmol/L
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HbA1c ≤ 7.5%
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Serum albumin ≥ 30 g/L
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INR ≤ 1.2
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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:
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Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days
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Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption
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Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors
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Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome
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Active or uncontrolled infections or serious illnesses or medical conditions
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Clinically significant liver diseases
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History of lung disease or history of opportunistic infections
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Type 1 or Type 2 diabetes mellitus requiring insulin
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Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia
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Known abnormalities in coagulation
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History of hypersensitivity to the study drugs or components
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Pregnant or lactating women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- MA40
- 2101
- M041883