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

International, Multicenter, Open-label, Treatment-extension Study for Subjects Who Completed a Phase 1 or Phase 2 Parental Study to Continue Receiving Treatment With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: SAR245408; Drug: SAR245409

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Investigational Site Number 056001
• France
  • Montpellier, France, 34295
    • Investigational Site Number 250004
  • Pierre Benite Cedex, France, 69495
    • Investigational Site Number 250003
  • Rouen Cedex, France, 76038
    • Investigational Site Number 250005
• Spain
  • Barcelona, Spain, 08035
    • Investigational Site Number 724001
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 840010
  • California
    • Los Angeles, California, United States, 90024
      • Investigational Site Number 840009
    • Los Angeles, California, United States, 90033
      • Investigational Site Number 840008
  • Colorado
    • Denver, Colorado, United States, 80262
      • Investigational Site Number 840022
  • Florida
    • Fort Myers, Florida, United States, 33919
      • Investigational Site Number 840104
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Investigational Site Number 840006
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 840004
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigational Site Number 840021
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Investigational Site Number 840002
  • Ohio
    • Canton, Ohio, United States, 44718
      • Investigational Site Number 840020
    • Columbus, Ohio, United States, 43210
      • Investigational Site Number 840015
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Investigational Site Number 840017
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Investigational Site Number 840007
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 840003
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 840005
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Investigational Site Number 840018

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: SAR245408; Pharmaceutical form: capsule or tablet Route of administration: oral
Experimental: 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).	Drug: SAR245408; Pharmaceutical form: capsule or tablet Route of administration: oral
Experimental: 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).	Drug: SAR245409; Pharmaceutical form: capsule or tablet Route of administration: oral
Experimental: 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).	Drug: SAR245409; Pharmaceutical form: capsule or tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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.	From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters	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.	From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Biochemical Parameters	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.	From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2012
• Primary Completion (Actual): May 23, 2018
• Study Completion (Actual): May 23, 2018

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TED12414; 2011-006140-78 (EudraCT Number); U1111-1124-1403 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No