FUnctional selection of advanced breast cancer patients for Talazoparib treatment Using the REpair Capacity (RECAP) test: The FUTURE trial
- Conditions
- breast carcinomaBreastcancer10006291
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 78
• Age >=18 years
• WHO performance status 0-2
• Locally advanced breast cancer without curative intent or metastatic breast
cancer
* The breast cancer must be either
o high grade (Bloom & Richardson grade 3) ER positive (>10%) and HER2 negative
primary breast cancer, or
o triple negative (ER<10%, PR<10% and HER2 negative), or
o 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 or
* the patient must have a proven germline or somatic BRCA1 and/or BRCA2 mutation
• The site of the metastatic lesion (or primary tumor in case it is still in
situ) should be easily amendable for biopsy. NB lung metastases (high risk of
hemato/pneumo-thorax) and bone metastases (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 planned.
• 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).
• 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.
• Measureable or evaluable disease according to RECIST 1.1 criteria (appendix 2)
• Life expectancy >= 3 months
• Hemoglobin >= 10 g/dL (6,2 mmol/L) and ANC of >= 1.5 x 109 /L
• Platelets >100 x 10e9/L
• 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
• Renal function as defined by serum creatinine <= 1.5 x ULN or creatinine
clearance >= 50 mL/min (by Cockcroft-Gault formula);
• Negative pregnancy test (urine/serum) for female patients with childbearing
potential;
• Written informed consent
• Any psychological condition potentially hampering compliance with the study
protocol
• 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
• 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
• Known persistent (>4 weeks) >= Grade 2 toxicity from prior cancer therapy
(except for alopecia grade 2)
• 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
• Women who have a positive pregnancy test (urine/serum) and/or who are
breastfeeding;
• 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)
• Concomitant use with P-gp inhibitors or inducers or BCRP inhibitors
• Any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia
(AML)
• Uncontrolled infectious disease (such as Human Immunodeficiency Virus
HIV-1 or HIV-2 infection) or known active hepatitis B or C
• Recent myocardial infarction (< six months) or unstable angina
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The aim of the current study is to assess the predictive potential of the RECAP<br /><br>test for in vivo response to talazoparib treatment by investigating the<br /><br>percentage of patients with HRD breast tumors with PFS on talazoparib<br /><br>monotherapy of 4 months or longer. The main endpoint is thus the proportion of<br /><br>patients with PFS at 4 months (PFS4). </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are overall response rate (ORR), overall survival (OS)<br /><br>among patients with HRD tumors treated with talazoparib. The negative<br /><br>predictive value will be determined within the HRP group.</p><br>