S 81694 Plus Paclitaxel in Metastatic Breast Cancer

NCT ID: NCT03411161

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-04
• Study Completion Date: 2020-06-08

Brief Summary

The purpose of this study is to determine the safety profile, the maximum tolerated dose (MTD) and the associated dose-limiting toxicities (DLTs) of S 81694 in combination with paclitaxel in metastatic breast cancer (mBC) patients, and to investigate the antitumour activity of the combination in metastatic triple negative breast cancer (mTNBC) patients.

Conditions

Metastatic Breast Cancer; Metastatic Triple Negative Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination therapy (S81694 + paclitaxel) phase I

Phase I: Single arm, non-randomized study in metastatic breast cancer patients. S81694 given intravenously every two weeks at different doses on D1 and D15 last for 28 days. The participants will also receive paclitaxel intravenously on D1, D8 and D15 last for 28 days.

Group Type: EXPERIMENTAL

Combination therapy (S81694 + paclitaxel) phase I

Intervention Type: DRUG

Dose escalation S 81694 (IV); paclitaxel started at 80 mg/m²,(IV)

paclitaxel phase II

Phase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients.

Paclitaxel given intravenously on D1, D8, and D15 at 80 mg/m² during a 28-day cycle.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Paclitaxel (IV) at 80 mg/m²/week

Combination therapy (S81694 + paclitaxel) phase II

Phase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients.

S 81694 given intravenously on D1 and D15 at recommended phase 2 dose (RP2D). Paclitaxel given intravenously on D1, D8, and D15 during a 28-day cycle.

Group Type: EXPERIMENTAL

Combination therapy (S81694 + paclitaxel) phase II

Intervention Type: DRUG

S 81694 (IV) at RP2D; paclitaxel (IV) at 80 mg/m²/week

Interventions

Combination therapy (S81694 + paclitaxel) phase I

Dose escalation S 81694 (IV); paclitaxel started at 80 mg/m²,(IV)

Intervention Type: DRUG

Paclitaxel

Paclitaxel (IV) at 80 mg/m²/week

Intervention Type: DRUG

Combination therapy (S81694 + paclitaxel) phase II

S 81694 (IV) at RP2D; paclitaxel (IV) at 80 mg/m²/week

Intervention Type: DRUG

Eligibility 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 (investigational medicinal product) 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario CAMPONE, Pr

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie de l'Ouest site Saint Herblain

Locations

Institut Jules Bordet Clinique Oncologie Médicale

Brussels, , Belgium

UZ Leuven Campus Gasthuisberg Dept. of General Medical

Leuven, , Belgium

Institut de Cancérologie de l'Ouest site Saint Herblain

Saint-Herblain, , France

Chiba cancer center Breast surgery

Chiba, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Erasmus MC Section Clinical Pharmacology

Rotterdam, , Netherlands

Countries

Belgium; France; Japan; Netherlands

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: study-level clinical trial data

View Document

Other Identifiers

2017-002459-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-81694-003

Identifier Type: -

Identifier Source: org_study_id