SAR240550 in Combination With Gemcitabine/Cisplatin in Non-small Cell Lung Cancer

NCT ID: NCT01086254

Last Updated: 2013-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-12-31

Brief Summary

Primary Objective:

• to assess the objective response rate (ORR) of Iniparib (SAR240550) administered as a 60-min intravenous infusion twice weekly, when combined to gemcitabine/cisplatin chemotherapy regimen (GCS) as well as with the standard regimen of gemcitabine/cisplatin (GC) in patients with stage IV non small cell lung cancer.

Secondary objectives are:

• to assess the safety profiles of the study combination GCS and of the standard regimen GC;
• to assess the progression free survival and the overall survival in both arms;
• to assess the relationship between DNA repair pathway characteristics of tumors at baseline and clinical outcome of disease.
• to assess the effect of Iniparib on PAR level in peripheral blood mononuclear cells (PBMC). (As of 10 September 2010, the collection of PBMC is temporarily discontinued.)

Detailed Description

The duration of the study for a patient will include a period for inclusion of up to 3 weeks. The patients may continue treatment up to a maximum of 6 cycles or until disease progression, unacceptable toxicity or consent withdrawal, followed by a minimum of 30-day follow-up after the last study treatment administration.

Patients will be followed for at least 30 days after the last administration of study treatment for safety purpose. In case of study treatment discontinuation without disease progression, efficacy data will be collected every 6 weeks until disease progression, death or end of study whatever comes first. After disease progression, the patient will be followed-up every 12 weeks (3 months) for overall survival (OS) until death or end of study whatever comes first.

The end of the study will be one year after the first dose of the last treated patient.

Conditions

Non-small Cell Lung Cancer Stage IV

Study Design

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

Study Groups

Iniparib/ Gemcitabine/ Cisplatin

Iniparib, 5.6 mg/kg, 60-min IV infusion twice weekly (days 1, 4, 8, and 11). Infusion starts after completion of GC regimen administration.

Gemcitabine, 1250 mg/m2, 30-min IV infusion on day 1 and day 8 and cisplatin 75mg/m², 3- to 4-hour IV infusion on day 1 of each 3-week cycle after the end of gemcitabine infusion.

Group Type: EXPERIMENTAL

Iniparib

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: 60-minute IV infusion

gemcitabine

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: 30-minute IV infusion

cisplatin

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: 1- to 4-hour IV infusion, according to the local standard

Gemcitabine/ Cisplatin

Gemcitabine, 1250 mg/m2, 30-min IV infusion on day 1 and day 8 and cisplatin 75mg/m², 3- to 4-hour IV infusion on day 1 of each 3-week cycle after the end of gemcitabine infusion.

Group Type: ACTIVE_COMPARATOR

gemcitabine

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: 30-minute IV infusion

cisplatin

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: 1- to 4-hour IV infusion, according to the local standard

Interventions

Iniparib

Pharmaceutical form: solution for infusion

Route of administration: 60-minute IV infusion

Intervention Type: DRUG

gemcitabine

Pharmaceutical form: solution for infusion

Route of administration: 30-minute IV infusion

Intervention Type: DRUG

cisplatin

Pharmaceutical form: solution for infusion

Route of administration: 1- to 4-hour IV infusion, according to the local standard

Intervention Type: DRUG

Other Intervention Names

SAR240550; BSI-201

Eligibility Criteria

Inclusion Criteria

• Stage IV disease (including stage IIIB with pleural effusion) with no prior systemic therapy. Adjuvant therapy is allowed if ended more than 1 year before inclusion in the study.
• Histologically confirmed squamous cell bronchogenic carcinoma OR non squamous cell carcinoma.
• Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the selected measurable lesions are outside the original radiation therapy port. Radiation therapy must have been completed >4 weeks prior to study entry.
• Palliative radiotherapy must have been completed > 2 weeks prior to study entry. Irradiated lesions may not serve as measurable lesions.
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate bone marrow reserve.
• Adequate liver and renal function.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.

Exclusion Criteria

• Prior treatment with gemcitabine, platinum salts or any PARP inhibitor class compound.
• Past or current history of neoplasm other than the entry diagnosis, with the exception of treated non-melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone and with an expected disease-free survival of > or = 5 years.
• Major medical conditions that might affect study participation e.g. cardiac disease, uncontrolled infection (>Grade 2).
• Presence of active brain metastases.
• A major surgical procedure, open biopsy, or significant traumatic injury within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
• Any history of medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results
• Grade 2 or higher ear and labyrinth disorders.
• Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.

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

• Minimum Eligible Age: 18 Years
• 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

Sanofi-Aventis Investigational Site Number 250002

Caen, , France

Sanofi-Aventis Investigational Site Number 250003

Marseille, , France

Sanofi-Aventis Investigational Site Number 250004

Toulouse, , France

Sanofi-Aventis Investigational Site Number 250001

Villejuif, , France

Sanofi-Aventis Investigational Site Number 276003

Essen, , Germany

Sanofi-Aventis Investigational Site Number 276002

Gauting, , Germany

Sanofi-Aventis Investigational Site Number 276001

Großhansdorf, , Germany

Sanofi-Aventis Investigational Site Number 380003

Livorno, , Italy

Sanofi-Aventis Investigational Site Number 380001

Orbassano, , Italy

Sanofi-Aventis Investigational Site Number 380002

Rozzano, , Italy

Sanofi-Aventis Investigational Site Number 724001

Badalona, , Spain

Sanofi-Aventis Investigational Site Number 724002

Barcelona, , Spain

Sanofi-Aventis Investigational Site Number 826001

Newcastle upon Tyne, , United Kingdom

Sanofi-Aventis Investigational Site Number 826002

Wolverhampton, , United Kingdom

Countries

France; Germany; Italy; Spain; United Kingdom

References

Novello S, Besse B, Felip E, Barlesi F, Mazieres J, Zalcman G, von Pawel J, Reck M, Cappuzzo F, Ferry D, Carcereny E, Santoro A, Garcia-Ribas I, Scagliotti G, Soria JC. A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer. Ann Oncol. 2014 Nov;25(11):2156-2162. doi: 10.1093/annonc/mdu384. Epub 2014 Aug 19.

Reference Type: DERIVED

PMID: 25139550 (View on PubMed)

Other Identifiers

2009-017270-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1116-5404

Identifier Type: OTHER

Identifier Source: secondary_id

TCD11420

Identifier Type: -

Identifier Source: org_study_id