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

NCT ID: NCT01587040

Last Updated: 2022-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-20
• Study Completion Date: 2018-05-23

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.

Conditions

Neoplasm Malignant

Study Design

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

Study Groups

SAR245408: Monotherapy

Participants 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).

Group Type: EXPERIMENTAL

SAR245408

Intervention Type: DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

SAR245408: Combination Regimen

Participants 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).

Group Type: EXPERIMENTAL

SAR245408

Intervention Type: DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

SAR245409: Monotherapy

Participants 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).

Group Type: EXPERIMENTAL

SAR245409

Intervention Type: DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

SAR245409: Combination Regimen

Participants 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).

Group Type: EXPERIMENTAL

SAR245409

Intervention Type: DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

Interventions

SAR245408

Pharmaceutical form: capsule or tablet Route of administration: oral

Intervention Type: DRUG

SAR245409

Pharmaceutical form: capsule or tablet Route of administration: oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

I 01. Males or females enrolled in Phase 1 or Phase 2 studies of SAR245408 or SAR245409 as monotherapy or in combination with other regimens who had completed data collection for the primary endpoint(s) of the parental study or who were being treated beyond the parental study cut-off and meet all the criteria to continue to be treated per the parental protocol.

I 02. All sexually active participants (male and female) must agreed to continue to use accepted methods of barrier contraception (i.e., condoms) during the course of the study and for 3 months after discontinuation of study treatment. For women of childbearing potential and for men who could father a child, a second method of contraception in addition to a barrier method is recommended. Hormonal contraception should be avoided in participants taking SAR245408 due to possible drug-drug interaction.

I 03. Female participants of childbearing potential must had a negative pregnancy test at baseline. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to other causes, including prior chemotherapy, anti-estrogens, or ovarian suppression.

Exclusion Criteria

E 01. The participant discontinued the parental study due to toxicity. E 02. Ongoing Grade 3 or higher Adverse Event (AE). E 03. Ongoing Serious Adverse Event (SAE). E 04. Participants with ongoing dose interruption for any reason unless the participant fulfilled the criteria in the parental protocol for restarting IMP. In such case participant started the treatment-extension study on Day 1 of the initiation period.

E 05. The participant had any of the following laboratory values ≥ Common Terminology of Adverse Events (CTCAE) Grade 3

• Absolute neutrophil count (ANC),
• Platelet count,
• Hemoglobin,
• Bilirubin,
• Serum creatinine or calculated creatinine clearance,
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
• Fasting plasma glucose (FPG),
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT).

E 06. The participant had a baseline corrected QT interval (QTc) >481 millisecond (msec) or if a participant has had a QTc interval increase of ≥ 60 msec from parental protocol baseline to an absolute value of > 470 msec.

E 07. The participant had a known allergy or hypersensitivity to components of the study treatment formulation(s).

E 08. The participant was pregnant or breastfeeding.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840010

Birmingham, Alabama, United States

Investigational Site Number 840009

Los Angeles, California, United States

Investigational Site Number 840008

Los Angeles, California, United States

Investigational Site Number 840022

Denver, Colorado, United States

Investigational Site Number 840104

Fort Myers, Florida, United States

Investigational Site Number 840006

Augusta, Georgia, United States

Investigational Site Number 840004

Boston, Massachusetts, United States

Investigational Site Number 840021

St Louis, Missouri, United States

Investigational Site Number 840002

New Brunswick, New Jersey, United States

Investigational Site Number 840020

Canton, Ohio, United States

Investigational Site Number 840015

Columbus, Ohio, United States

Investigational Site Number 840017

Philadelphia, Pennsylvania, United States

Investigational Site Number 840007

Nashville, Tennessee, United States

Investigational Site Number 840003

Dallas, Texas, United States

Investigational Site Number 840005

San Antonio, Texas, United States

Investigational Site Number 840018

Morgantown, West Virginia, United States

Investigational Site Number 056001

Leuven, , Belgium

Investigational Site Number 250004

Montpellier, , France

Investigational Site Number 250003

Pierre-Bénite, , France

Investigational Site Number 250005

Rouen, , France

Investigational Site Number 724001

Barcelona, , Spain

Countries

United States; Belgium; France; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2011-006140-78

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1124-1403

Identifier Type: OTHER

Identifier Source: secondary_id

TED12414

Identifier Type: -

Identifier Source: org_study_id