The primary objective of this study is determining the feasibility of the ex vivo HRD test in metastatic lesions of different sites among breast cancer patients who will start treatment with chemotherapy. The sites of metastatic lesions that will be…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The ability of ex vivo assay for RAD51 IRIF formation (as a measure of
homologous recombination deficiency (HRD)) in metastatic breast cancer lesions
of different sites among advanced breast cancer patients before start of
treatment with chemotherapy. The sites of metastatic lesions that will be
investigated are: liver, lymph nodes, and subcutaneous lesions. For each
localization, biopsies from at least 3 different patients will be collected.
Secondary outcome
-
Background summary
Defective homologous recombination DNA repair imposed by BRCA1 or BRCA2 gene
deficiencies sensitizes cells to double strand break (DSB)-inducing DNA
damaging agents like platinum derivates and anthracyclines. The formation of
RAD51 IRIF is impaired in BRCA1 or BRCA2 defective cells and also in other
genetic defects leading to HR deficiency. In current healthcare these
anti-cancer agents e.g. platinum derivates are usually administered at late
stage of advanced breast cancer from which only a subpopulation of patients
benefit from the treatment. Having a test that can predict whether or not an
individual patient could benefit from the treatment will provide the option to
provide the treatment at an earlier stage of the disease.
Study objective
The primary objective of this study is determining the feasibility of the ex
vivo HRD test in metastatic lesions of different sites among breast cancer
patients who will start treatment with chemotherapy. The sites of metastatic
lesions that will be investigated are: liver, lymph nodes, bone and
subcutaneous lesions.
In case feasible, the preclinical predictive value of this test for
response to double strand break-inducing DNA damaging agents will be confirmed
in a clinical study among breast cancer patients who will be treated with
DSB-inducing agents correlating the test results to a clinical response rate to
the given treatment. The findings of this pilot study are conditional for
setting up such a clinical study.
Study design
Pilot study
Study burden and risks
Burden for the patient will be minimal because only easily approachable
metastatic lesions will be offered for a biopsy. Bone and lung metastasis will
be excluded from this study to avoid risks and side effects. Expected but
confined effects will be mild pain and in the worst case a(n extended) bleeding
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
• Breast cancer patients with distant metastases who preferably are planned to receive systemic treatment (e.g. cisplatin, carboplatin, anthracyclins and alkylating agents), alone or in combination with other chemotherapeutic agents.
• The site of the tumor should be amendable for biopsy. NB lung metastases (high risk of hematothorax) and bone metastases (not suitable for ex vivo test because calcifications interfere with experimental procedures) are excluded.
• Age > 18 years
• WHO performance status 0 or 1
• Bilirubin <1.5 ULN and both AST and ALT <2,5x ULN in case a liver biopsy is planned
• Platelets > 100 x 10e9/L
• INR <1.5
• Written informed consent
Exclusion criteria
• Current therapeutically use of anti-coagulant (coumarin derivates, warfarin, heparin or low molecular weight heparin [LMWH]) whereby a short interruption of drug use is not allowed. LMWH if used for prophylaxis is allowed.
• Any psychological condition potentially hampering compliance with the study protocol
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49306.078.14 |