The primary objective of this study is to assess the objective response rate (ORR, the percentage of treated patients in whom the tumor significantly reduces in size or becomes non-detectable) of SAR240550 administered as a 60min intravenous…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective response rate. The ORR will be evaluated every second cycle.
Secondary outcome
Efficacy
- Clinical benefit rate (CBR): the percentage treated patients of whom the
tumor is stable, decreases in size or becomes undetectable for >=24 weeks.
- Progression-free survival and total survival.
Safety
Safety will be assessed by standard clinical and laboratory tests (hematology,
serum chemistry). Toxicity grade is defined by the NCI CTC AE v 4.0.
Molecular-biological properties and pharmacokinetics
In a substudiy which is optional for the patients the following evaluations
will be performed:
-Pharmacogenetic properties of the tumor (including BRCA1 and BRCA2) <=1 month
before the first treatment and at the end of the first cycle. For this purpose
tumor biopsies will be performed.
-Pharmacodynamics; by means of blood sampling (in the first 6 weeks of
treatment) the amount of PAR (poly-(ADP-ribose)) will be analyzed.
-Pharmacokinetics; by means of blood sampling (in the first 6 weeks of
treatment) the pharmacokinetic profile of SAR240550 will be determined.
Background summary
Breast cancer remains the most common malignancy in women worldwide with more
than 1.2
million cases diagnosed every year and 500 000 deaths per year. Routine
assessment of three cellular receptors (estrogen receptor [ER], progesterone
receptor [PR], and human epidermal growth factor 2 [HER2]) are biomarkers that
are being used for predicting patient response to therapies.
However, up to 20% of breast cancers are negative for expression of all three
receptors. Despite best available therapy, TNBC continues to be associated with
poorer outcomes when compared to other breast cancer subtypes, and is
associated with a higher chance on metastases. No treatment has been registered
specifically for TNBC.
SAR240550 is a first-in-class investigational targeted therapy designed to
inhibit poly-(ADPribose)
polymerase (PARP1). PARP1 is an enzyme involved in DNA damage repair, and
inhibition of this enzyme can prevent tumor cells from recovering from
DNA-damage. This can cause the tumor cells to die by apoptosis or make them
more vulnerable to chemotherapy.
Study objective
The primary objective of this study is to assess the objective response rate
(ORR, the percentage of treated patients in whom the tumor significantly
reduces in size or becomes non-detectable) of SAR240550 administered as a 60min
intravenous infusion twice weekly (arm A) or weekly (arm B), in combination
with gemcitabine/carboplatin chemotherapy regimen in patients with metastasized
TNBC. Secundary objective are the safety profile and (in a subset of the
patients) the molecular biological profile of the tumor and the pharmacokinetic
profile of SAR240550.
Study design
This is an open label, randomised study.
Intervention
Patients will be randomly assigned in one of the two treatment arms.
Arm A: Each treatment cycle of 3 weeks the patient will receive a 60-minut
intravenous treatment of 5,6 mg/kg SAR240550 on day 1, 4, 8, and 11.
Arm B: Each treatment cycle of 3 weeks the patient will receive a 60-minut
intravenous treatment of 11.2 mg/kg SAR240550 on day 1, and 8.
In both treatment arms the patients will receive treatment with gemcitabine and
carboplatin on day 1 and 8. Treatment will continue every 3 weeks in the
absence of disease progression or unacceptable toxicity.
Depending on the treatment arm the patient will receive intravenous treatment
in the hospital 2-4 times per 3-week cycle. From all patients blood samples
will be taken on days 1 and 8 of each cycle for standard hematological and
biochemical analysis. Every 6 weeks a CT-imaging will be performed to determine
the status of the tumor(s).
Study burden and risks
The adverse events of gemcitabine (Gemzar®) and carboplatine (Carbosin®) are
well known since these products have been registered for the treatment of
several types of tumors for a number of years now.
So far SAR240550 (BS201) has been administered as single agent to about 37
patients and as a combination therapy to about 238 patients. From the latter
group about 60 patients had TNBC and were treated in combination with
gemcatibine and carboplatin.
Safety data provided to date demonstrates that the addition of SAR240550 to
gemcitabine/carboplatin did not potentiate toxicities of
gemcitabine/carboplatin alone.
Depending on the treatment arm the patient will receive intravenous treatment
in the hospital 2-4 times per 3-week cycle. From all patients blood samples
will be taken on days 1 and 8 of each cycle for standard hematological and
biochemical analysis. Every 6 weeks a CT-imaging will be performed to determine
the status of the tumor(s).
If the patient chooses to participate in the substudy, she may be asked to stay
overnight twice during the first cycle. For this substudy 26 (arm A) or 22 (arm
B) extra bloodsamples are required. The total amount of blood is 78 (arm A) or
66(arm B) milliliters.
Kampenringweg 45 d-e
2803 PE Gouda
NL
Kampenringweg 45 d-e
2803 PE Gouda
NL
Listed location countries
Age
Inclusion criteria
* Histologically documented breast cancer that is ER- negative, PR-negative, and HER2 non-overexpressing with metastases measurable by RECIST 1.1 criteria
* Prior treatment that includes:
- never having received anticancer therapy for metastatic disease OR
- having received 1 or 2 prior chemotherapy regimens in the metastatic setting;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
* Good organ and marrow function (see protocol page 32 for laboratory values)
* Radiation therapy completed at least 7 days before study dosing on day 1;
*Central nervous system (CNS) metastases allowed under certain conditions (see protocol page 32)
* No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a malignancy diagnosed and curatively treated >5 years ago)
Exclusion criteria
*Systemic anticancer therapy within 14 days of the first dose of study drug;
*Prior treatment with gemcitabine, carboplatin, cisplatin or any PARP inhibitor;
*Has not recovered to grade 1 from AEs per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0;
*Bone metastasis or skin metastasis only;
*Major medical conditions that might affect study participation (e.g., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);
*Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation is acceptable;
* Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2009-016091-80-NL |
| CCMO | NL30484.078.09 |
| Other | Zie sectie J |