Trial Title:
FUnctional Selection of Advanced Breast Cancer Patients for Talazoparib Treatment Using the REpair Capacity (RECAP) Test
NCT ID:
NCT06193525
Condition:
Advanced Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Talazoparib
Conditions: Keywords:
Metastatic Breast Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Talazoparib
Description:
Talazoparib is administered daily as single agent, 1 mg orally until unacceptable
toxicity or progression of disease.
Arm group label:
Talazoparib
Other name:
Talazoparib 1 MG Oral Capsule [Talzenna]
Summary:
The goal of this clinical trial is to prove that the RECAP test is capable of selecting
advanced breast cancer patients sensitive for treatment with the PARP inhibitor
talazoparib. Participants will undergo an ultrasound-guided biopsy and a blood
withdrawal. Homologous Recombination (HR) deficient patients (approximately 30%) can
start talazoparib treatment until progression of the disease or unacceptable side-effects
and their response will be evaluated.
Detailed description:
This is a single arm, prospective multicenter study among patients with advanced breast
cancer with RECAP-based HRD phenotype who will be treated with talazoparib, a strong PARP
inhibitor. After signing informed consent, metastatic breast cancer patients will undergo
an ultrasound (or CT-) guided biopsy in order to obtain at least two biopsies from a
metastatic lesion to determine the HR status by the RECAP test and a blood withdrawal for
ctDNA isolation. HR proficient (HRP) patients will receive anti-tumor therapy (non study
drug) on discretion of their treating physician; only the response on treatment will be
registered. Approximately 30% of screened patients will have an HRD tumor and thus will
be eligible to start talazoparib monotherapy until PD or unacceptable side effects. The
primary endpoint is PFS at four months. Additional endpoints will include overall
response rate and overall survival. Upon progression, patients will be kindly asked for
consent to perform another biopsy (optional) and blood withdrawal in order to prove
reversibility of the RECAP test outcome (from HRD to HRP) and explore potential
mechanisms of resistance (both in tissue and ctDNA).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- WHO performance status 0-2
- Locally advanced breast cancer without options for treatment with curative intent or
metastatic breast cancer
- Objective progressive disease (PD) according to RECIST within 4 months prior to
study entry
- The breast cancer must be either
- high grade (Bloom & Richardson grade 3) ER positive (>10%) and HER2 negative
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 or
- the patient must have a proven germline or somatic BRCA1 and/or BRCA2
mutation The Bloom & Richardson grading is always based on the primary
tumor. The receptor status can be based on the primary tumor or a
metastatic lesion whichever comes latest.
- 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 r estarting 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 (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.
- Measurable 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 or <5 x ULN in case of liver metastasis
- Adequate renal function as defined by either 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
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 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. Patients completely free of symptoms
and without corticosteroids for at least four weeks after adequate treatment by
resection and/or irradiation could be eligible (consult PI).
- 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 of P-gp inhibitors or inducers or BCRP inhibitors (see Appendix A)
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Leiden University Medical Center
Address:
City:
Leiden
Zip:
2333ZA
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Clinical Trial Center
Phone:
+31107041566
Email:
secretariaatctc@erasmusmc.nl
Contact backup:
Last name:
J R Kroep, MD, PhD
Phone:
+31715263523
Email:
j.r.kroep@lumc.nl
Investigator:
Last name:
J R Kroep, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Erasmus Medical Center
Address:
City:
Rotterdam
Zip:
3015GD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Clinical Trial Center
Phone:
+31107041566
Email:
secretariaatctc@erasmusmc.nl
Investigator:
Last name:
Agnes Jager, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Groningen University Medical Center
Address:
City:
Groningen
Zip:
9713GZ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Clinical Trial Center
Phone:
+31107041566
Email:
secretariaatctc@erasmusmc.nl
Contact backup:
Last name:
M Jalving, MD, PhD
Phone:
+31503616161
Email:
m.jalving@umcg.nl
Investigator:
Last name:
M Jalving, MD, PhD
Email:
Principal Investigator
Start date:
September 16, 2019
Completion date:
December 2025
Lead sponsor:
Agency:
Erasmus Medical Center
Agency class:
Other
Collaborator:
Agency:
Leiden University Medical Center
Agency class:
Other
Collaborator:
Agency:
University Medical Center Groningen
Agency class:
Other
Source:
Erasmus Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06193525
