Metastatic Breast Cancer (mBC) and metastatic Triple Negative Breast Cancer (mTNBC) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: S81694
Product Code: S81694
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Not available
Current Sponsor code: S 81694
Concentration unit: mg mill
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Phase I : - Histologically or cytologically confirmed metastatic breast cancer, refractory to any standard therapy or for which the standard therapy is considered unsuitable; - Patient must have at least one evaluable or measurable metastatic lesion (lesions as defined by revised Response Evaluation Criteria in Solid Tumors For Phase II : - Histologically or cytologically confirmed advanced inoperable triple negative breast cancer with no prior anticancer therapy regimen in metastatic setting; - Patient with a minimum washout period of 12 months following previous taxane based adjuvant therapy; - Patient must have at least one measurable metastatic lesion. Ascites, pleural effusion, and bone metastases are not considered measurable; - Acceptance of pre-treatment metastatic biopsies for all patients and on-treatment metastatic biopsies in selected centres. For the whole study: - Male or female subjects aged = 18 years old, or legal age of the majority in the country; - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; - Estimated life expectancy of at least 3 months; - Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP administration; -Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration; - Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration; - Female participant of childbearing potential must have a negative pregnancy test (serum) within 7 days prior to the first day of test drug administration. Effective contraception both for female patients of childbearing potential and male patients with parteners of childbearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 78
Exclusion criteria
Exclusion criteria: - Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer or intra-mucosal gastro-intestinal cancers that were treated curatively); - Presence of grade = 2 toxic effects (excluding alopecia) due to prior cancer therapy; - Known hypersensitivity to the IMP (S 81694 and paclitaxel) or their excipients; - Evidence of peripheral neuropathy of grade 2 or higher; - Participant previously received paclitaxel and discontinued due to toxicity related to paclitaxel; - Participant known as refractory to taxanes; - Any prior cancer therapy within 4 weeks or 5 half-life (whichever is the shorter) before the first IMP administration; - Participant with current, serious, uncontrolled infections; - Participant with brain metastasis or leptomeningeal metastasis (except patients with brain metastasis that have been stable post-radiation therapy and who are off steroids for > 2 months); - History of cardiac disease; - Uncontrolled arterial hypertension; - Presence of risk factors for torsades de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome); - Any clinically significant medical condition (e.g. organ dysfunction) or laboratory abnormality likely to jeopardize the patient’s safety or to interfere with the conduct of the study, in the investigator’s opinion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For Phase I: -To determine the safety profile and tolerability of S 81694 given in combination with paclitaxel by assessment of the DLT and the MTD based on safety data described using Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 in patients with mBC. - To establish the recommended phase II dose (RP2D) of S 81694 in combination with paclitaxel. For phase II: - To evaluate Progression Free Survival (PFS).;Secondary Objective: For phase I: -To characterize the plasma pharmacokinetic (PK) profiles of S 81694 and its metabolites (if applicable) and of paclitaxel in combination. - To investigate any preliminary antitumour activity of this combination. For phase II: - To assess the anti-tumour activity using Response Evaluation Criteria In Solid Tumours version 1.1 in terms of: o Objective Response Rate (ORR), o Response duration (RD), o Overall survival (OS). - To characterize the safety and tolerability of S 81694 in combination with paclitaxel at RP2D according to NCI-CTCAE v4.03. - To characterize the plasma PK profiles of S 81694 and of paclitaxel and its metabolites (if applicable) in combination.;Primary end point(s): For phase I : - incidence of DLTs occuring during the first cycle. - Safety and tolerability of S 81694 in combination with paclitaxel assessed by: o Incidence and severity of AEs and SAEs, o Laboratory tests (haematology, haemolysis, biochemistry, urinary analysis and pregnancy test), o Vital signs and weight, o Physical examination and performance status, o ECG parameters, o Dose interruptions, dose reductions and dose intensity. For phase II : - Progression-Free Survival is defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression according to RECIST v1.1 or death due to any cause.;Timepoint(s) of evaluation of this end point: For Phase I : All over the study For Phase II : At inclusion and during the study at the end of cycle 2, then | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For phase I: - PK parameters of S 81694 and paclitaxel plasma concentration Tumour response assessed by RECIST v1.1. For phase II : - Objective Response Rate (ORR); - Response duration (RD); - Overall survival; - Safety and tolerability of S 81694 in combination with paclitaxel or with paclitaxel alone assessed by: o Incidence and severity of AEs and SAEs, o Laboratory tests (haematology, haemolysis biochemistry, urinary analysis and pregnancy test), o Vital signs and weight, o Physical examination and performance status, o ECG parameters, o Dose interruptions, dose reductions and dose intensity. - PK parameters of S 81694 and paclitaxel concentrations.;Timepoint(s) of evaluation of this end point: All over the study | — |
Countries
Belgium, France, Japan, Netherlands
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed