Clinical Trials /

S 81694 Plus Paclitaxel in Metastatic Breast Cancer

NCT03411161

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: S 81694 Plus Paclitaxel in Metastatic Breast Cancer
  • Official Title: Phase I/II Trial of S 81694 Administered Intravenously in Combination With Paclitaxel to Evaluate the Safety, Pharmacokinetic and Efficacy in Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CL1-81694-003
  • SECONDARY ID: 2017-002459-27
  • NCT ID: NCT03411161

Conditions

  • Metastatic Breast Cancer
  • Metastatic Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Combination therapy (S81694 + paclitaxel) phase ICombination therapy (S81694 + paclitaxel) phase I
Paclitaxelpaclitaxel
Combination therapy (S81694 + paclitaxel) phase IICombination therapy (S81694 + paclitaxel) phase II

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Combination therapy (S81694 + paclitaxel) phase IExperimentalPhase I: Single arm, non-randomized study in metastatic breast cancer patients. S81694 given intravenously at different doses on D1, D8 and D15 last for 28 days. The participants will also receive paclitaxel intravenously on D1, D8 and D15 last for 28 days.
  • Combination therapy (S81694 + paclitaxel) phase I
paclitaxelActive ComparatorPhase 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.
  • Paclitaxel
Combination therapy (S81694 + paclitaxel) phase IIExperimentalPhase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients. S 81694 given intravenously on D1, D8 and D15 at recommended phase 2 dose (RP2D). paclitaxel given intravenously on D1, D8, and D15 at RP2D.
  • Combination therapy (S81694 + paclitaxel) phase II

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs (dose-limiting toxicities)
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety criterion - A DLT is defined as any toxicity attributable to S81694 or the combination that occurs before the end of Cycle 1

Secondary Outcome Measures

Measure:The PK (pharmacokinetic) profile of S 81694 and paclitaxel plasma concentration : Area under the plasma concentration-time curve (AUC)
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety and tolerability criteria
Measure:The PK profile of S 81694 and paclitaxel plasma concentration : Elimination half-life (T½)
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety and tolerability criteria
Measure:The PK profile of S 81694 and paclitaxel plasma concentration : Maximum plasma concentration (Cmax)
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety and tolerability criteria
Measure:The PK profile of S 81694 and paclitaxel plasma concentration : Minimum plasma concentration (Cmin)
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety and tolerability criteria
Measure:Overall Response Rate (ORR) [ based on Investigator review of the images according to RECIST 1.1]
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Efficacy criterion
Measure:Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03
Time Frame:Through study completion, an average of 3 years
Safety Issue:
Description:Safety criterion

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Institut de Recherches Internationales Servier

Trial Keywords

  • Mps1
  • Mps1i
  • S81694
  • breast cancer
  • triple negative breast cancer
  • phase I
  • phase II

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