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)
- Conditions
- Squamous Cell Lung Cancer
- Interventions
- Drug: gemcitabine/carboplatin
- Registration Number
- NCT01082549
- Lead Sponsor
- Sanofi
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 780
Eligible patients must meet the following criteria to be enrolled in the study:
-
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).
-
Patients who have received prior adjuvant therapy for early-stage lung cancer are eligible if at least 12 months have elapsed from that treatment.
-
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.
-
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.
-
Presence of evaluable (measureable or non-measurable) disease.
-
ECOG Performance Status of 0 or 1.
-
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.
-
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.
-
>18 years of age.
-
Ability to understand the nature of this study, give written informed consent, and comply with study requirements.
-
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.
-
Prior treatment with gemcitabine, carboplatin (except in the adjuvant setting), or Iniparib.
-
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.
-
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.
-
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.
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Women who are pregnant or lactating.
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Any serious, active infection (> Grade 2) at the time of treatment.
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A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
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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.
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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.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description gemcitabine/carboplatin gemcitabine/carboplatin - gemcitabine/carboplatin plus Iniparib gemcitabine/carboplatin plus Iniparib -
- Primary Outcome Measures
Name Time Method overall survival 12 months, 24 months
- Secondary Outcome Measures
Name Time Method progression free survival 12 months
Trial Locations
- Locations (142)
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 840309
🇺🇸Loma Linda, California, United States
Investigational Site Number 840104
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840213
🇺🇸Augusta, Georgia, United States
Investigational Site Number 840347
🇺🇸Augusta, Georgia, United States
Investigational Site Number 840305
🇺🇸Marietta, Georgia, United States
Investigational Site Number 840314
🇺🇸Tucker, Georgia, United States
Investigational Site Number 840337
🇺🇸Royal Oak, Michigan, United States
Investigational Site Number 840106
🇺🇸Columbia, South Carolina, United States
Investigational Site Number 840103
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 840322
🇺🇸Morgantown, West Virginia, United States
Investigational Site Number 840207
🇺🇸Huntsville, Alabama, United States
Investigational Site Number 840343
🇺🇸Athens, Georgia, United States
Investigational Site Number 840218
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840217
🇺🇸Lakeland, Florida, United States
Investigational Site Number 840339
🇺🇸La Verne, California, United States
Investigational Site Number 840326
🇺🇸Stockton, California, United States
Investigational Site Number 840210
🇺🇸Bridgeton, Missouri, United States
Investigational Site Number 840211
🇺🇸West Reading, Pennsylvania, United States
Investigational Site Number 840203
🇺🇸Collierville, Tennessee, United States
Investigational Site Number 840316
🇺🇸Wichita, Kansas, United States
Investigational Site Number 348001
🇭🇺Mátraháza, Hungary
Investigational Site Number 616006
🇵🇱Bialystok, Poland
Investigational Site Number 348004
🇭🇺Nyíregyháza, Hungary
Investigational Site Number 616005
🇵🇱Wroclaw, Poland
Investigational Site Number 840329
🇺🇸South Bend, Indiana, United States
Investigational Site Number 840327
🇺🇸Maywood, California, United States
Investigational Site Number 380001
🇮🇹Novara, Italy
Investigational Site Number 380008
🇮🇹Orbassano, Italy
Investigational Site Number 840308
🇺🇸Scarborough, Maine, United States
Investigational Site Number 840335
🇺🇸Columbus, Ohio, United States
Investigational Site Number 376001
🇮🇱Tzrifin, Israel
Investigational Site Number 380006
🇮🇹Genova, Italy
Investigational Site Number 348003
🇭🇺Budapest, Hungary
Investigational Site Number 442001
🇱🇺Luxembourg, Luxembourg
Investigational Site Number 376005
🇮🇱Petah-Tikva, Israel
Investigational Site Number 376003
🇮🇱Tel Hashomer, Israel
Investigational Site Number 348005
🇭🇺Budapest, Hungary
Investigational Site Number 616001
🇵🇱Krakow, Poland
Investigational Site Number 376002
🇮🇱Kfar Saba, Israel
Investigational Site Number 616007
🇵🇱Lubin, Poland
Investigational Site Number 616004
🇵🇱Olsztyn, Poland
Investigational Site Number 826006
🇬🇧Wolverhampton, United Kingdom
Investigational Site Number 724008
🇪🇸Sevilla, Spain
Investigational Site Number 616008
🇵🇱Torun, Poland
Investigational Site Number 616002
🇵🇱Warszawa, Poland
Investigational Site Number 528006
🇳🇱Maastricht, Netherlands
Investigational Site Number 724007
🇪🇸Zaragoza, Spain
Investigational Site Number 840302
🇺🇸Cleveland, Ohio, United States
Investigational Site Number 840348
🇺🇸Cleveland, Ohio, United States
Investigational Site Number 840312
🇺🇸Seattle, Washington, United States
Investigational Site Number 840313
🇺🇸Chicago, Illinois, United States
Investigational Site Number 528004
🇳🇱Eindhoven, Netherlands
Investigational Site Number 528001
🇳🇱Groningen, Netherlands
Investigational Site Number 528003
🇳🇱Zwolle, Netherlands
Investigational Site Number 840303
🇺🇸San Diego, California, United States
Investigational Site Number 840318
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840330
🇺🇸Durham, North Carolina, United States
Investigational Site Number 840105
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840101
🇺🇸Nashville, Tennessee, United States
Investigational Site Number 840205
🇺🇸Orlando, Florida, United States
Investigational Site Number 380003
🇮🇹Roma, Italy
Investigational Site Number 380002
🇮🇹Perugia, Italy
Investigational Site Number 380007
🇮🇹Roma, Italy
Investigational Site Number 826005
🇬🇧Leeds, United Kingdom
Investigational Site Number 840306
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840336
🇺🇸Denver, Colorado, United States
Investigational Site Number 642004
🇷🇴Craiova, Romania
Investigational Site Number 642005
🇷🇴Hunedoara, Romania
Investigational Site Number 642002
🇷🇴Alba Iulia, Romania
Investigational Site Number 642006
🇷🇴Bucuresti, Romania
Investigational Site Number 642001
🇷🇴Cluj Napoca, Romania
Investigational Site Number 840202
🇺🇸Bethesda, Maryland, United States
Investigational Site Number 840212
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 840317
🇺🇸Duarte, California, United States
Investigational Site Number 840310
🇺🇸Vallejo, California, United States
Investigational Site Number 840307
🇺🇸Los Angeles, California, United States
Investigational Site Number 840321
🇺🇸Santa Rosa, California, United States
Investigational Site Number 840315
🇺🇸Newark, Delaware, United States
Investigational Site Number 840216
🇺🇸Ft. Lauderdale, Florida, United States
Investigational Site Number 840346
🇺🇸Norwich, Connecticut, United States
Investigational Site Number 840215
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840201
🇺🇸Gainesville, Georgia, United States
Investigational Site Number 840301
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840319
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840345
🇺🇸Salisbury, Maryland, United States
Investigational Site Number 840328
🇺🇸St. Louis Park, Minnesota, United States
Investigational Site Number 840204
🇺🇸Morristown, New Jersey, United States
Investigational Site Number 840220
🇺🇸Spartanburg, South Carolina, United States
Investigational Site Number 840311
🇺🇸Bend, Oregon, United States
Investigational Site Number 840208
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 840323
🇺🇸Fort Worth, Texas, United States
Investigational Site Number 840219
🇺🇸Newport News, Virginia, United States
Investigational Site Number 056004
🇧🇪Brugge, Belgium
Investigational Site Number 056003
🇧🇪Brussel, Belgium
Investigational Site Number 840331
🇺🇸Wauwatosa, Wisconsin, United States
Investigational Site Number 056001
🇧🇪Liège, Belgium
Investigational Site Number 840344
🇺🇸Tacoma, Washington, United States
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
🇨🇦Quebec, Canada
Investigational Site Number 250007
🇫🇷Brest, France
Investigational Site Number 124001
🇨🇦Toronto, Canada
Investigational Site Number 250003
🇫🇷Marseille, France
Investigational Site Number 250009
🇫🇷Limoges Cedex, France
Investigational Site Number 250002
🇫🇷Dijon, France
Investigational Site Number 250004
🇫🇷Paris Cedex 13, France
Investigational Site Number 276007
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 250010
🇫🇷Pierre Benite Cedex, France
Investigational Site Number 250008
🇫🇷Poitiers, France
Investigational Site Number 250006
🇫🇷Strasbourg, France
Investigational Site Number 250001
🇫🇷Saint-Herblain Cedex, France
Investigational Site Number 250005
🇫🇷Tours Cedex 1, France
Investigational Site Number 276002
🇩🇪Amberg, Germany
Investigational Site Number 276004
🇩🇪Berlin, Germany
Investigational Site Number 276009
🇩🇪Immenhausen, Germany
Investigational Site Number 276012
🇩🇪Heidelberg, Germany
Investigational Site Number 276008
🇩🇪Großhansdorf, Germany
Investigational Site Number 276010
🇩🇪Halle/Saale, Germany
Investigational Site Number 276003
🇩🇪Oldenburg, Germany
Investigational Site Number 276001
🇩🇪Löwenstein, Germany
Investigational Site Number 276006
🇩🇪München, Germany
Investigational Site Number 724005
🇪🇸Madrid, Spain
Investigational Site Number 528005
🇳🇱Breda, Netherlands
Investigational Site Number 724009
🇪🇸Badalona, Spain
Investigational Site Number 724003
🇪🇸Barcelona, Spain
Investigational Site Number 724006
🇪🇸Madrid, Spain
Investigational Site Number 724002
🇪🇸Málaga, Spain
Investigational Site Number 724004
🇪🇸La Coruña, Spain
Investigational Site Number 724001
🇪🇸Palma De Mallorca, Spain
Investigational Site Number 826002
🇬🇧Glasgow, United Kingdom
Investigational Site Number 724010
🇪🇸Valencia, Spain
Investigational Site Number 826001
🇬🇧Manchester, United Kingdom
Investigational Site Number 840320
🇺🇸Louisville, Kentucky, United States
Investigational Site Number 840350
🇺🇸Chapel Hill, North Carolina, United States
Investigational Site Number 840352
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 840102
🇺🇸Richmond, Virginia, United States