Clinical trial NCT02984683: Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer
Official title: Open-label Phase 2 Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-12-07
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6 (membrane intensity of 2+, 3+ in greater than or equal to (\>=) 30% of tumor cells) treated at the selected dose in an expanded cohort, in addition to the participants treated in Part 1. - Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.

Secondary Objectives:

To assess:

* Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP).
* The impact of ocular primary prophylaxis on the incidence of keratopathies.
* The potential immunogenicity of SAR566658.
* To evaluate the global safety profile.

Detailed description: The duration of the study for 1 participant included a screening period of up to 21 days prior to first study drug administration, 3-week treatment cycle(s) (until 30 days after last SAR566658 administration), and a follow-up period. Each participant was treated until radiological disease progression, unacceptable toxicity, or participant's refusal of further study treatment.

Eligibility criteria: Inclusion criteria :

* Measurable Metastatic TNBC.
* Participants with CA6-positive disease.
* Participants received at least 1 prior chemotherapy regimen but no more than 3 for advanced/metastatic disease.
* Prior anticancer therapy must have contained anthracycline (eg, doxorubicin), if not contraindicated, and a taxane (eg, docetaxel, paclitaxel) in an adjuvant/neo-adjuvant or metastatic setting.

Exclusion criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status \>=2.
* Participant less than 18 years old.
* Pregnant or breast-feeding women.
* Participants with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of study drug.
* Wash out period of less than 3 weeks or 5 half-lives from previous antitumor chemotherapy, immunotherapy, or any investigational treatment.
* History of brain metastasis (other than totally resected or previously irradiated and nonprogressive/relapsed), spinal cord compression or carcinomatous meningitis, or new evidence of brain leptomeningeal disease.
* Prior treatment with eribulin as last prior therapy or prior maytansinoid treatments (DM1 or DM4 antibody-drug conjugates \[ADCs\]).
* Known intolerance to infused protein products including other monoclonal antibodies and ADCs.
* Poor bone marrow reserve and/or poor organ function.
* Symptomatic peripheral neuropathy Grade \>=2.
* Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute nonrecurrent corneal conditions.
* Participants wearing contact lenses who are not willing to stop wearing them for the duration of the study.
* Medical conditions requiring concomitant administration of strong Cytochrome P450 3A4 (CYP3A4) inhibitors, unless it could be discontinued at least 2 weeks before 1st administration of SAR566658.
* Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings
timeFrame: Up to Cycle 2 (each cycle of 21 days)
measure: Percentage of Participants With Objective Response
timeFrame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
Secondary outcomes:
measure: Percentage of Participants With Disease Control
timeFrame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
measure: Duration of Response (DOR)
timeFrame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
measure: Progression Free Survival (PFS)
timeFrame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
measure: Time to Tumor Progression (TTP)
timeFrame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
measure: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)
timeFrame: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)
measure: Number of Participants With Keratopathies (Corneal Toxicity)
timeFrame: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)
measure: Number of Participants With Positive Anti-SAR566658 Antibodies Response
timeFrame: Up to 3 treatment cycles, each cycle 21 days
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Investigational Site Number 0560001
city: Praha 2
country: Czechia
facility: Investigational Site Number 2030002
city: Genova
country: Italy
facility: Investigational Site Number 3800003
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Roma
country: Italy
facility: Investigational Site Number 3800004
city: Maastricht
country: Netherlands
facility: Investigational Site Number 5280001
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 5280002
city: Barcelona
country: Spain
facility: Investigational Site Number 7240002
city: Lleida
country: Spain
facility: Investigational Site Number 7240005
city: Madrid
country: Spain
facility: Investigational Site Number 7240001
city: Madrid
country: Spain
facility: Investigational Site Number 7240006
city: Sevilla
country: Spain
facility: Investigational Site Number 7240003
city: Valencia
country: Spain
facility: Investigational Site Number 7240004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: