Advanced or metastatic breast cancer
Conditions
Interventions
Product Name: Talazoparib
Pharmaceutical Form: Capsule
INN or Proposed INN: TALAZOPARIB
Current Sponsor code: PF-06944076
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration nu
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Age =18 years ? WHO performance status 0-2 ? Advanced breast cancer ? Patients must have (had) a high grade (Bloom & Richardson grade 3) ER positive (>10%) and HER2 negative primary breast cancer or a triple negative (ER/PR100 x 10e9/L and INR =65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: ? 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 x8 Gy for pain palliation, then seven days interval after the last radiation should be maintained ? Patients who have received a PARP inhibitor previously for advanced setting ? 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 if all other in- and exclusion criteria are obeyed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove that the RECAP test is capable of selecting advanced breast cancer patients sensitive for treatment with the PARP inhibitor talazoparib as measured by the PFS rate at 4 months.;Secondary Objective: 1. To determine overall response rate and overall survival among HRD tumors treated with talazoparib. 2. To explore differences in molecular aberrations in HR genes (e.g. BRCA1/2, PALB2) between HRD tumors that respond and those that do not respond to talazoparib. Moreover, to determine whether non-BRCA1/2 or BRCA1 promoter methylated HRD tumors respond differently to talazoparib than BRCA1/2 mutated HRD tumors. 3. To explore mechanisms of reversion of the HRD phenotype by comparing paired biopsies before treatment and upon progression on talazoparib. 4. To unravel resistance mechanisms by sequencing a DNA repair gene panel on circulating tumor DNA (ctDNA) pretreatment and at disease progression.;Primary end point(s): 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). ;Timepoint(s) of evaluation of this end point: 4 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are overall response rate (ORR), overall survival (OS) among patients with HRD tumors treated with talazoparib.;Timepoint(s) of evaluation of this end point: Two monthly until progressive disease | — |
Countries
Netherlands
Contacts
Public ContactClinical Trial Center
Erasmus MC Cancer Institute
Outcome results
None listed