FUnctional selection of advanced breast cancer patients for Talazoparib treatment Using the REpair Capacity (RECAP) test: The FUTURE trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Sep 2019 → 22 Apr 2025

Decision date (initial)

2025-01-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer

External identifiers

EU CT number

2024-518036-36-03

EudraCT number

2018-002914-10

ClinicalTrials.gov

NCT06193525

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Diagnosis

To prove that the RECAP test has the potential of selecting patients who are sensitive to treatment with the PARP inhibitor talazoparib as measured by the PFS rate at 4 months

Conditions and MedDRA coding

Breast cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Age > 18years
2. WHO performance status 0-2
3. Locally advanced breast cancer without curative intent or metastatic breast cancer
4. The breast cancer must be either: high grade (Bloom & Richardson grade 3) ER positive (>10%) and HER2 negatieve primary breast cancer, or triple negative (ER <10%, PR<10% and HER2 negative) or any Bloom & Richardson grading and receptor status and also at least one metastatic lesion must have a proven HRD phenotype based on a RECAP test not treated with anticancer therapy thereafter of the patient must have a proven germline or somatic BRCA1 and/or BRCA2 mutation
5. The site of the metastatic lesion (or primary tymor in case it is still in situ) should be easily amendable for biopsy. NB. lung metastases (high risk of hemato/pneumo-thorax) and bone metatases (not suitable for RECAP test because calcifications interfere with experimental procedures) are excluded. The local guidelines will be used for stopping and restarting of anticoagulation. Bilirubin <1.5 ULN (except elevated bilirubin due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin) and both AST and ALT <5x ULN in case a liver biopsy is plannend.
6. The tumor must be HRD, defined as HRD identified by the RECAP test determined just before the start of potential Talazoparib treatment within this study or just (also in case a proven germline BRCA1/2 mutation is present)
7. Maximum of four prior lines of chemotherapy for advanced disease; Patients who received platinum compounds are eligible if they have had at least a progression free interval of four months.
8. Measureable or evaluable disease according to RECIST 1.1 criteria (appendix 2)
9. Life expectancy ≥ 3 months
10. Hemoglobin ≥ 10 g/dL (6,2 mmol/L) and ANC of ≥ 1.5 x 109 /L
11. Platelets >100 x 10e9/L
12. Hepatic function as defined by total serum bilirubin ≤ 1. 5 x ULN (except elevated bilirubin due to Gilbert’s disease or a similar syndrome involving slow conjugation of bilirubin), ASAT and ALAT < 3 x ULN
13. Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
14. Negative pregnancy test (urine/serum) for female patients with childbearing potential;
15. Written informed consent

Exclusion criteria 11

1. Any psychological condition potentially hampering compliance with the study protocol
2. Any treatment with investigational antitumor drugs within 28 days prior to receiving the first dose of investigational treatment; or within 21 days for standard chemotherapy; or within 14 days for weekly scheduled chemotherapeutic regimens or endocrine therapy
3. Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1 or 2 x 8 Gy for pain palliation, then seven days interval after the last radiation should be maintained
4. Known persistent (>4 weeks) ≥ Grade 2 toxicity from prior cancer therapy (except for alopecia grade 2)
5. Symptomatic brain or leptomeningeal metastases. If adequately treated with resection and/or irradiation and patients are at least four weeks completely free of symptoms of these metastases without the use of corticosteroids, patients could be eligible
6. Women who have a positive pregnancy test (urine/serum) and/or who are breastfeeding;
7. Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence)
8. Concomitant use with P-gp inhibitors or inducers or BCRP inhibitors
9. Any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
10. Uncontrolled infectious disease (such as Human Immunodeficiency Virus HIV-1 or HIV-2 infection) or known active hepatitis B or C
11. Recent myocardial infarction (< six months) or unstable angina

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The aim of the current study is to assess the predictive potential of the RECAP test for in vivo response to talazoparib treatment by investigating the percentage of patients with HRD breast tumors with PFS on talazoparib monotherapy of 4 months or longer. The main endpoint is thus the proportion of patients with PFS at 4 months (PFS4).

Secondary endpoints 1

1. Secondary endpoints are overall response rate (ORR), overall survival (OS) among patients with HRD tumors treated with talazoparib. The negative predictive value will be determined within the HRP group.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Mandy van Rosmalen

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Mandy van Rosmalen

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications