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S 81694 Plus Paclitaxel in Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03411161
Recruitment Status : Completed
First Posted : January 26, 2018
Last Update Posted : July 8, 2020
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Metastatic Triple Negative Breast Cancer Drug: Combination therapy (S81694 + paclitaxel) phase I Drug: Paclitaxel Drug: Combination therapy (S81694 + paclitaxel) phase II Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study will be conducted in two successive parts:

  • a dose escalation phase I part, which is a single arm, non-randomised and non-comparative study in patient with mBC
  • a randomised phase II part, which is a two-arm, randomised study at RP2D (recommended phase II dose), to evaluate the efficacy and the safety of S 81694 in combination with paclitaxel (experimental arm) versus paclitaxel alone (comparator arm) in untreated mTNBC
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 4, 2018
Actual Primary Completion Date : June 8, 2020
Actual Study Completion Date : June 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: 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.
Drug: Combination therapy (S81694 + paclitaxel) phase I
Dose escalation S 81694 (IV); paclitaxel started at 80 mg/m²,(IV)

Active Comparator: 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.

Drug: Paclitaxel
Paclitaxel (IV) at 80 mg/m²/week

Experimental: 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.

Drug: Combination therapy (S81694 + paclitaxel) phase II
S 81694 (IV) at RP2D; paclitaxel (IV) at 80 mg/m²/week




Primary Outcome Measures :
  1. Incidence of DLTs (dose-limiting toxicities) [ Time Frame: Through study completion, an average of 4 years ]
    Safety criterion - A DLT is defined as any toxicity attributable to S81694 or the combination that occurs before the end of Cycle 1

  2. Safety and tolerability assessed by incidence of Adverse Events [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03

  3. Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria disease progression according to RECIST v1.1 or death due to any cause

  4. Abnormalities in physical examination and performance status (ECG) (mm/s) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria

  5. Abnormalities in blood pressure (mmHg) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

  6. Abnormalities in heart rate (BPM (beat per minute)) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

  7. Abnormalities in body temperature (C°degree celsius) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

  8. Abnormalities in respiration rate (cycles per minute) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

  9. Abnormalities in body weight (Kg) [ Time Frame: Through study completion, an average of 4 years ]
    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

  10. Progression free survival (PFS) [based on Investigator review of the images according to RECIST 1.1] [ Time Frame: Through study completion, an average of 4 years ]
    Efficacy criterion - time from the date of first study drug intake until the date of the investigator-assessed disease progression or death due to any cause whichever occurs first.


Secondary Outcome Measures :
  1. 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 and tolerability criteria

  2. 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 and tolerability criteria

  3. 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 and tolerability criteria

  4. 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 and tolerability criteria

  5. Overall Response Rate (ORR) [ based on Investigator review of the images according to RECIST 1.1] [ Time Frame: Through study completion, an average of 4 years ]
    Efficacy criterion

  6. Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03 [ Time Frame: Through study completion, an average of 4 years ]
    Safety criterion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03411161


Locations
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Belgium
Institut Jules Bordet Clinique Oncologie Médicale
Bruxelles, Belgium, 1000
UZ Leuven Campus Gasthuisberg Dept. of General Medical
Leuven, Belgium, 3000
France
Institut de Cancérologie de l'Ouest site Saint Herblain
Saint Herblain, France, 44805
Japan
Chiba cancer center Breast surgery
Chiba, Japan, 2608717
Osaka International Cancer Institute
Osaka, Japan, 5418567
Netherlands
Erasmus MC Section Clinical Pharmacology
Rotterdam, Netherlands, 30145
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Investigators
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Principal Investigator: Mario CAMPONE, Pr Institut de Cancérologie de l'Ouest site Saint Herblain
Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT03411161    
Other Study ID Numbers: CL1-81694-003
2017-002459-27 ( EudraCT Number )
First Posted: January 26, 2018    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: https://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
Mps1
Mps1i
S81694
breast cancer
triple negative breast cancer
phase I
phase II
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action