Clinical trial NCT01587040: Open Label Treatment Extension Study With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neoplasm Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-04-27
Enrollment: 61
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters
timeFrame: From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Biochemical Parameters
timeFrame: From Baseline up to 30 days after the last dose (maximum exposure: 1959 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840010
state: Alabama
city: Los Angeles
country: United States
facility: Investigational Site Number 840009
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840008
state: California
city: Denver
country: United States
facility: Investigational Site Number 840022
state: Colorado
city: Fort Myers
country: United States
facility: Investigational Site Number 840104
state: Florida
city: Augusta
country: United States
facility: Investigational Site Number 840006
state: Georgia
city: Boston
country: United States
facility: Investigational Site Number 840004
state: Massachusetts
city: Saint Louis
country: United States
facility: Investigational Site Number 840021
state: Missouri
city: New Brunswick
country: United States
facility: Investigational Site Number 840002
state: New Jersey
city: Canton
country: United States
facility: Investigational Site Number 840020
state: Ohio
city: Columbus
country: United States
facility: Investigational Site Number 840015
state: Ohio
city: Philadelphia
country: United States
facility: Investigational Site Number 840017
state: Pennsylvania
city: Nashville
country: United States
facility: Investigational Site Number 840007
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 840003
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840005
state: Texas
city: Morgantown
country: United States
facility: Investigational Site Number 840018
state: West Virginia
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: Montpellier
country: France
facility: Investigational Site Number 250004
city: Pierre Benite Cedex
country: France
facility: Investigational Site Number 250003
city: Rouen Cedex
country: France
facility: Investigational Site Number 250005
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: