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

NCT01587040 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: TED124142011-006140-78U1111-1124-1403
• Study Type: interventional
• Target: 61
• Locations: 4 countries
• Sites: 21

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.

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (3)

• 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)

Study Arms (4)

SAR245408: Monotherapy

EXPERIMENTAL

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

SAR245408: Combination Regimen

EXPERIMENTAL

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

SAR245409: Monotherapy

EXPERIMENTAL

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

SAR245409: Combination Regimen

EXPERIMENTAL

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

Interventions

SAR245408 DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

SAR245408: Combination Regimen; SAR245408: Monotherapy

SAR245409 DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

SAR245409: Combination Regimen; SAR245409: Monotherapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (21)

Investigational Site Number 840010

Birmingham, Alabama, 35205, United States

Location

Investigational Site Number 840009

Los Angeles, California, 90024, United States

Location

Investigational Site Number 840008

Los Angeles, California, 90033, United States

Location

Investigational Site Number 840022

Denver, Colorado, 80262, United States

Location

Investigational Site Number 840104

Fort Myers, Florida, 33919, United States

Location

Investigational Site Number 840006

Augusta, Georgia, 30912, United States

Location

Investigational Site Number 840004

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840021

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840002

New Brunswick, New Jersey, 08903, United States

Location

Investigational Site Number 840020

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840015

Columbus, Ohio, 43210, United States

Location

Investigational Site Number 840017

Philadelphia, Pennsylvania, 19111, United States

Location

Investigational Site Number 840007

Nashville, Tennessee, 37232, United States

Location

Investigational Site Number 840003

Dallas, Texas, 75230, United States

Location

Investigational Site Number 840005

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 840018

Morgantown, West Virginia, 26506, United States

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 250004

Montpellier, 34295, France

Location

Investigational Site Number 250003

Pierre-Bénite, 69495, France

Location

Investigational Site Number 250005

Rouen, 76038, France

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Neoplasms

Interventions

XL147; XL765

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2012
• First Posted: April 27, 2012
• Study Start: July 20, 2012
• Primary Completion: May 23, 2018
• Study Completion: May 23, 2018
• Last Updated: April 19, 2022
• Results First Posted: June 11, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); FR (3); BE (1); US (16)