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Open Label Treatment Extension Study With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen

Phase 1
Completed
Conditions
Neoplasm Malignant
Interventions
Registration Number
NCT01587040
Lead Sponsor
Sanofi
Brief Summary

Primary Objective:

The purpose of this study was to determine the long term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in participants who were benefiting from treatment.

Detailed Description

The duration of the study for an individual participant included:

1. Baseline assessments: within 7 days prior to the first dose of investigational medicinal product (IMP).

2. Study treatment period(s):

Participants started study treatment at the beginning of the initiation or extension periods based on the length of prior therapy with SAR245408 or SAR245409

* if \<2 cycles, started with initiation period; Participant must have had completed all the visits in the initiation period before moving to the extension period.

* if \>=2 cycles, started with extension period; duration of extension period was unlimited.

* Participants who took a SAR245408 or SAR245409 daily dose higher than their established dose of SAR245408 or SAR245409, respectively, in the parental study entered the study on Day 1 of the initiation period.

* Participants who had dose interrupted in the parental study but fulfilled parental protocol criteria to restart IMP treatment entered the treatment-extension study on Day 1 of the initiation period.

* Participants who fulfilled the parental study criteria for IMP treatment continuation but had ongoing Grade 2 adverse events (AEs) entered the treatment-extension study on Day 1 of the initiation period.

Participants continued to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 or SAR245409 were available to them outside of the clinical trial.

3. Follow-up assessments: 23 to 37 days after the last dose of IMP.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
61
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR245408: MonotherapySAR245408Participants received SAR245408 400 milligrams (mg) once daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days).
SAR245409: MonotherapySAR245409Participants received SAR245409 50 mg twice daily or at the established dose as monotherapy in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days).
SAR245409: Combination RegimenSAR245409Participants received SAR245409 50 mg twice daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245409 were available (up to 1917 days). Commercially available drugs were used as combination medications with SAR245409 (depending on the parental study, the following drugs were used in combination with SAR245409: letrozole, temozolomide, rituximab, bendamustine and rituximab).
SAR245408: Combination RegimenSAR245408Participants received SAR245408 400 mg once daily or at the established dose as combination regimen in the parental study until disease progression, unacceptable toxicity, withdrawal of consent, or until commercial supplies of SAR245408 were available (up to 1959 days). Commercially available drugs were used as combination medications with SAR245408 (depending on the parental study, the following drugs were used in combination with SAR245408: paclitaxel and carboplatin, letrozole, trastuzumab, paclitaxel and trastuzumab).
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Events (TEAEs)From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. Serious adverse event (SAE): any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs: AEs that developed/worsened/became serious during on-treatment period (time from IMP until 30 days after last dose of any IMP). Any TEAE included participants with both SAE \& non-SAEs. TEAE included participants with any treatment-emergent SAE (TESAE). TEAEs that led to death, dose reduction and/or delay, discontinuation \& AEs related to treatment were reported. Grades (3=severe, 4=life-threatening/disabling) represents severity of AEs.

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological ParametersFrom Baseline up to 30 days after the last dose (maximum exposure: 1959 days)

Hematological parameters assessed were anemia, neutropenia and thrombocytopenia. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Biochemical ParametersFrom Baseline up to 30 days after the last dose (maximum exposure: 1959 days)

Biochemical parameters assessed were hyperglycemia, aspartate aminotransferase (ASAT) increased, alanine aminotransferase (ALAT) increased, hyperbilirubinemia, hypocalcemia, creatinine increased. Parameters were assessed as per the NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (21)

Investigational Site Number 840104

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Fort Myers, Florida, United States

Investigational Site Number 840008

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Los Angeles, California, United States

Investigational Site Number 840006

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Augusta, Georgia, United States

Investigational Site Number 840009

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Los Angeles, California, United States

Investigational Site Number 840004

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Boston, Massachusetts, United States

Investigational Site Number 840002

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New Brunswick, New Jersey, United States

Investigational Site Number 840021

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Saint Louis, Missouri, United States

Investigational Site Number 840020

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Canton, Ohio, United States

Investigational Site Number 840015

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Columbus, Ohio, United States

Investigational Site Number 840003

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Dallas, Texas, United States

Investigational Site Number 840017

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Philadelphia, Pennsylvania, United States

Investigational Site Number 840018

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Morgantown, West Virginia, United States

Investigational Site Number 250003

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Pierre Benite Cedex, France

Investigational Site Number 250005

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Rouen Cedex, France

Investigational Site Number 724001

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Barcelona, Spain

Investigational Site Number 056001

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Leuven, Belgium

Investigational Site Number 250004

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Montpellier, France

Investigational Site Number 840007

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Nashville, Tennessee, United States

Investigational Site Number 840010

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Birmingham, Alabama, United States

Investigational Site Number 840022

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Denver, Colorado, United States

Investigational Site Number 840005

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San Antonio, Texas, United States

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