Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects With Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC)

NCT ID: NCT01082549

Last Updated: 2016-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 780 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2013-04-30

Brief Summary

To evaluate the overall survival (OS) of patients with advanced squamous cell lung cancer receiving the combination of gemcitabine/carboplatin either with or without Iniparib.

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

Conditions

Squamous Cell Lung Cancer

Study Design

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

Study Groups

gemcitabine/carboplatin

Group Type: ACTIVE_COMPARATOR

gemcitabine/carboplatin

Intervention Type: DRUG

i.v.

gemcitabine/carboplatin plus Iniparib

Group Type: EXPERIMENTAL

gemcitabine/carboplatin plus Iniparib

Intervention Type: DRUG

i.v.

Interventions

gemcitabine/carboplatin

i.v.

Intervention Type: DRUG

gemcitabine/carboplatin plus Iniparib

i.v.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Eligible patients must meet the following criteria to be enrolled in the study:

1. Newly diagnosed, stage IV squamous cell lung cancer. This includes patients who present with disseminated metastases, and those with a malignant pleural or pericardial effusion (i.e., formerly stage IIIB in the 6th TNM staging system).

2. Patients who have received prior adjuvant therapy for early-stage lung cancer are eligible if at least 12 months have elapsed from that treatment.

3. Histologically confirmed squamous cell bronchogenic carcinoma. Patients whose tumors contain mixed non-small cell histologies are eligible, as long as squamous carcinoma is the predominant histology. Mixed tumors with small cell anaplastic elements are not eligible. Cytologic specimens obtained by brushings, washings, or needle aspiration of the defined lesion are acceptable.

4. Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation therapy port. Radiation therapy must have been completed >4 weeks prior to the initiation of study treatment. Patients who have received chemo/radiation for locally advanced NSCLC are not eligible. Patients who have received palliative radiation therapy for symptomatic metastases must have completed treatment >14 days prior the initiation of the study treatment.

5. Presence of evaluable (measureable or non-measurable) disease.

6. ECOG Performance Status of 0 or 1.

7. Laboratory values as follows:

• Absolute neutrophil count (ANC) >1,500/microL and platelets >100,000/microL (≤72 hours prior to initial treatment).
• Hemoglobin >9 g/dL (Note: Patients may be transfused or receive erythropoietin to maintain or exceed this level).
• Bilirubin < ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement.
• Creatinine <2.0 mg/dL, or creatinine clearance >40 mL/min (as calculated by the Cockcroft-Gault method.

8. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment and at least 6 months after the last dose of the study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Sexually active men must agree to use a medically acceptable form of birth control during treatment and at least 6 months after the last dose. If a female partner becomes pregnant during the course of the study the treating physician should be informed immediately.

9. >18 years of age.

10. Ability to understand the nature of this study, give written informed consent, and comply with study requirements.

11. Patients entering this study must be willing to provide tissue from a previous tumor biopsy (if available) for correlative testing. An exception to this is when the national/local regulations prohibits some of the key activities of this research like the export of samples to third countries, storage of coded samples or global gene expression profiling without a pre-specified list of target genes. If tissue is not available, a patient will still be eligible for enrollment into the study.

Exclusion Criteria

1. Prior treatment with gemcitabine, carboplatin (except in the adjuvant setting), or Iniparib.

2. 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 any primary site, or invasive cancers treated definitively, with treatment ending >5 years previously and no evidence of recurrences.

3. A history of cardiac disease, as defined by:

• Malignant hypertension
• Unstable angina
• Congestive heart failure
• Myocardial infarction within the previous 6 months
• Symptomatic, unstable or uncontrolled, cardiac arrhythmias. Patients who have stable, rate-controlled atrial fibrillation are eligible for study enrollment.

4. Active brain metastases. Patients with treated brain metastases are eligible, if (1) radiation therapy was completed at least 2 weeks prior to study entry; (2) follow-up scan shows no disease progression; and (3) patient does not require steroids.

5. Women who are pregnant or lactating.

6. Any serious, active infection (> Grade 2) at the time of treatment.

7. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.

8. A major surgical procedure, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.

9. Uncontrolled or intercurrent illness including, that in the opinion of the investigator may increase the risks associated with study participation or administration of the investigational products, or that may interfere with the interpretation of the results.

10. History of any 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.

11. 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

Investigational Site Number 840306

Birmingham, Alabama, United States

Investigational Site Number 840207

Huntsville, Alabama, United States

Investigational Site Number 840351

Muscle Shoals, Alabama, United States

Investigational Site Number 840338

Anaheim, California, United States

Investigational Site Number 840353

Burbank, California, United States

Investigational Site Number 840341

Concord, California, United States

Investigational Site Number 840317

Duarte, California, United States

Investigational Site Number 840339

La Verne, California, United States

Investigational Site Number 840309

Loma Linda, California, United States

Investigational Site Number 840307

Los Angeles, California, United States

Investigational Site Number 840327

Maywood, California, United States

Investigational Site Number 840303

San Diego, California, United States

Investigational Site Number 840321

Santa Rosa, California, United States

Investigational Site Number 840326

Stockton, California, United States

Investigational Site Number 840310

Vallejo, California, United States

Investigational Site Number 840336

Denver, Colorado, United States

Investigational Site Number 840346

Norwich, Connecticut, United States

Investigational Site Number 840315

Newark, Delaware, United States

Investigational Site Number 840216

Fort Lauderdale, Florida, United States

Investigational Site Number 840215

Jacksonville, Florida, United States

Investigational Site Number 840217

Lakeland, Florida, United States

Investigational Site Number 840205

Orlando, Florida, United States

Investigational Site Number 840104

Sarasota, Florida, United States

Investigational Site Number 840343

Athens, Georgia, United States

Investigational Site Number 840213

Augusta, Georgia, United States

Investigational Site Number 840347

Augusta, Georgia, United States

Investigational Site Number 840201

Gainesville, Georgia, United States

Investigational Site Number 840301

Lawrenceville, Georgia, United States

Investigational Site Number 840305

Marietta, Georgia, United States

Investigational Site Number 840314

Tucker, Georgia, United States

Investigational Site Number 840313

Chicago, Illinois, United States

Investigational Site Number 840218

Evansville, Indiana, United States

Investigational Site Number 840319

Indianapolis, Indiana, United States

Investigational Site Number 840329

South Bend, Indiana, United States

Investigational Site Number 840316

Wichita, Kansas, United States

Investigational Site Number 840320

Louisville, Kentucky, United States

Investigational Site Number 840308

Scarborough, Maine, United States

Investigational Site Number 840202

Bethesda, Maryland, United States

Investigational Site Number 840345

Salisbury, Maryland, United States

Investigational Site Number 840337

Royal Oak, Michigan, United States

Investigational Site Number 840328

Saint Louis Park, Minnesota, United States

Investigational Site Number 840210

Bridgeton, Missouri, United States

Investigational Site Number 840212

Omaha, Nebraska, United States

Investigational Site Number 840318

Las Vegas, Nevada, United States

Investigational Site Number 840204

Morristown, New Jersey, United States

Investigational Site Number 840350

Chapel Hill, North Carolina, United States

Investigational Site Number 840330

Durham, North Carolina, United States

Investigational Site Number 840105

Cincinnati, Ohio, United States

Investigational Site Number 840302

Cleveland, Ohio, United States

Investigational Site Number 840348

Cleveland, Ohio, United States

Investigational Site Number 840335

Columbus, Ohio, United States

Investigational Site Number 840311

Bend, Oregon, United States

Investigational Site Number 840211

West Reading, Pennsylvania, United States

Investigational Site Number 840352

Charleston, South Carolina, United States

Investigational Site Number 840106

Columbia, South Carolina, United States

Investigational Site Number 840220

Spartanburg, South Carolina, United States

Investigational Site Number 840103

Chattanooga, Tennessee, United States

Investigational Site Number 840208

Chattanooga, Tennessee, United States

Investigational Site Number 840203

Collierville, Tennessee, United States

Investigational Site Number 840101

Nashville, Tennessee, United States

Investigational Site Number 840323

Fort Worth, Texas, United States

Investigational Site Number 840219

Newport News, Virginia, United States

Investigational Site Number 840102

Richmond, Virginia, United States

Investigational Site Number 840312

Seattle, Washington, United States

Investigational Site Number 840344

Tacoma, Washington, United States

Investigational Site Number 840322

Morgantown, West Virginia, United States

Investigational Site Number 840331

Wauwatosa, Wisconsin, United States

Investigational Site Number 056004

Bruges, , Belgium

Investigational Site Number 056003

Brussels, , Belgium

Investigational Site Number 056001

Liège, , Belgium

Investigational Site Number 124003

Edmonton, , Canada

Investigational Site Number 124006

Greenfield Park, , Canada

Investigational Site Number 124005

London, , Canada

Investigational Site Number 124007

Oshawa, , Canada

Investigational Site Number 124004

Québec, , Canada

Investigational Site Number 124001

Toronto, , Canada

Investigational Site Number 250007

Brest, , France

Investigational Site Number 250002

Dijon, , France

Investigational Site Number 250009

Limoges, , France

Investigational Site Number 250003

Marseille, , France

Investigational Site Number 250004

Paris, , France

Investigational Site Number 250010

Pierre-Bénite, , France

Investigational Site Number 250008

Poitiers, , France

Investigational Site Number 250001

Saint-Herblain, , France

Investigational Site Number 250006

Strasbourg, , France

Investigational Site Number 250005

Tours, , France

Investigational Site Number 276002

Amberg, , Germany

Investigational Site Number 276004

Berlin, , Germany

Investigational Site Number 276007

Frankfurt am Main, , Germany

Investigational Site Number 276008

Großhansdorf, , Germany

Investigational Site Number 276010

Halle, , Germany

Investigational Site Number 276012

Heidelberg, , Germany

Investigational Site Number 276009

Immenhausen, , Germany

Investigational Site Number 276001

Löwenstein, , Germany

Investigational Site Number 276006

München, , Germany

Investigational Site Number 276003

Oldenburg, , Germany

Investigational Site Number 348005

Budapest, , Hungary

Investigational Site Number 348003

Budapest, , Hungary

Investigational Site Number 348001

Mátraháza, , Hungary

Investigational Site Number 348004

Nyíregyháza, , Hungary

Investigational Site Number 376002

Kfar Saba, , Israel

Investigational Site Number 376005

Petah Tikva, , Israel

Investigational Site Number 376003

Tel Litwinsky, , Israel

Investigational Site Number 376001

Tzrifin, , Israel

Investigational Site Number 380006

Genova, , Italy

Investigational Site Number 380001

Novara, , Italy

Investigational Site Number 380008

Orbassano, , Italy

Investigational Site Number 380002

Perugia, , Italy

Investigational Site Number 380003

Roma, , Italy

Investigational Site Number 380007

Roma, , Italy

Investigational Site Number 442001

Luxembourg, , Luxembourg

Investigational Site Number 528005

Breda, , Netherlands

Investigational Site Number 528004

Eindhoven, , Netherlands

Investigational Site Number 528001

Groningen, , Netherlands

Investigational Site Number 528006

Maastricht, , Netherlands

Investigational Site Number 528003

Zwolle, , Netherlands

Investigational Site Number 616006

Bialystok, , Poland

Investigational Site Number 616001

Krakow, , Poland

Investigational Site Number 616007

Lubin, , Poland

Investigational Site Number 616004

Olsztyn, , Poland

Investigational Site Number 616008

Torun, , Poland

Investigational Site Number 616002

Warsaw, , Poland

Investigational Site Number 616005

Wroclaw, , Poland

Investigational Site Number 642002

Alba Iulia, , Romania

Investigational Site Number 642006

Bucharest, , Romania

Investigational Site Number 642001

Cluj-Napoca, , Romania

Investigational Site Number 642004

Craiova, , Romania

Investigational Site Number 642005

Hunedoara, , Romania

Investigational Site Number 724004

A Coruña, , Spain

Investigational Site Number 724009

Badalona, , Spain

Investigational Site Number 724003

Barcelona, , Spain

Investigational Site Number 724005

Madrid, , Spain

Investigational Site Number 724006

Madrid, , Spain

Investigational Site Number 724002

Málaga, , Spain

Investigational Site Number 724001

Palma de Mallorca, , Spain

Investigational Site Number 724008

Seville, , Spain

Investigational Site Number 724010

Valencia, , Spain

Investigational Site Number 724007

Zaragoza, , Spain

Investigational Site Number 826002

Glasgow, , United Kingdom

Investigational Site Number 826005

Leeds, , United Kingdom

Investigational Site Number 826001

Manchester, , United Kingdom

Investigational Site Number 826006

Wolverhampton, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Hungary; Israel; Italy; Luxembourg; Netherlands; Poland; Romania; Spain; United Kingdom

Other Identifiers

20090321

Identifier Type: OTHER

Identifier Source: secondary_id

EFC11553

Identifier Type: -

Identifier Source: org_study_id