Clinical trial NCT01082549: 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)
Official title: Randomized Phase 3 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Squamous Cell Lung Cancer
Keywords: Patients with Previously Untreated Advanced Squamous Cell Lung Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-03-08
Enrollment: 780
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: overall survival
timeFrame: 12 months, 24 months
Secondary outcomes:
measure: progression free survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840306
state: Alabama
city: Huntsville
country: United States
facility: Investigational Site Number 840207
state: Alabama
city: Muscle Shoals
country: United States
facility: Investigational Site Number 840351
state: Alabama
city: Anaheim
country: United States
facility: Investigational Site Number 840338
state: California
city: Burbank
country: United States
facility: Investigational Site Number 840353
state: California
city: Concord
country: United States
facility: Investigational Site Number 840341
state: California
city: Duarte
country: United States
facility: Investigational Site Number 840317
state: California
city: La Verne
country: United States
facility: Investigational Site Number 840339
state: California
city: Loma Linda
country: United States
facility: Investigational Site Number 840309
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840307
state: California
city: Maywood
country: United States
facility: Investigational Site Number 840327
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840303
state: California
city: Santa Rosa
country: United States
facility: Investigational Site Number 840321
state: California
city: Stockton
country: United States
facility: Investigational Site Number 840326
state: California
city: Vallejo
country: United States
facility: Investigational Site Number 840310
state: California
city: Denver
country: United States
facility: Investigational Site Number 840336
state: Colorado
city: Norwich
country: United States
facility: Investigational Site Number 840346
state: Connecticut
city: Newark
country: United States
facility: Investigational Site Number 840315
state: Delaware
city: Ft. Lauderdale
country: United States
facility: Investigational Site Number 840216
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840215
state: Florida
city: Lakeland
country: United States
facility: Investigational Site Number 840217
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840205
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 840104
state: Florida
city: Athens
country: United States
facility: Investigational Site Number 840343
state: Georgia
city: Augusta
country: United States
facility: Investigational Site Number 840213
state: Georgia
city: Augusta
country: United States
facility: Investigational Site Number 840347
state: Georgia
city: Gainesville
country: United States
facility: Investigational Site Number 840201
state: Georgia
city: Lawrenceville
country: United States
facility: Investigational Site Number 840301
state: Georgia
city: Marietta
country: United States
facility: Investigational Site Number 840305
state: Georgia
city: Tucker
country: United States
facility: Investigational Site Number 840314
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 840313
state: Illinois
city: Evansville
country: United States
facility: Investigational Site Number 840218
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Site Number 840319
state: Indiana
city: South Bend
country: United States
facility: Investigational Site Number 840329
state: Indiana
city: Wichita
country: United States
facility: Investigational Site Number 840316
state: Kansas
city: Louisville
country: United States
facility: Investigational Site Number 840320
state: Kentucky
city: Scarborough
country: United States
facility: Investigational Site Number 840308
state: Maine
city: Bethesda
country: United States
facility: Investigational Site Number 840202
state: Maryland
city: Salisbury
country: United States
facility: Investigational Site Number 840345
state: Maryland
city: Royal Oak
country: United States
facility: Investigational Site Number 840337
state: Michigan
city: St. Louis Park
country: United States
facility: Investigational Site Number 840328
state: Minnesota
city: Bridgeton
country: United States
facility: Investigational Site Number 840210
state: Missouri
city: Omaha
country: United States
facility: Investigational Site Number 840212
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 840318
state: Nevada
city: Morristown
country: United States
facility: Investigational Site Number 840204
state: New Jersey
city: Chapel Hill
country: United States
facility: Investigational Site Number 840350
state: North Carolina
city: Durham
country: United States
facility: Investigational Site Number 840330
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 840105
state: Ohio
city: Cleveland
country: United States
facility: Investigational Site Number 840302
state: Ohio
city: Cleveland
country: United States
facility: Investigational Site Number 840348
state: Ohio
city: Columbus
country: United States
facility: Investigational Site Number 840335
state: Ohio
city: Bend
country: United States
facility: Investigational Site Number 840311
state: Oregon
city: West Reading
country: United States
facility: Investigational Site Number 840211
state: Pennsylvania
city: Charleston
country: United States
facility: Investigational Site Number 840352
state: South Carolina
city: Columbia
country: United States
facility: Investigational Site Number 840106
state: South Carolina
city: Spartanburg
country: United States
facility: Investigational Site Number 840220
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 840103
state: Tennessee
city: Chattanooga
country: United States
facility: Investigational Site Number 840208
state: Tennessee
city: Collierville
country: United States
facility: Investigational Site Number 840203
state: Tennessee
city: Nashville
country: United States
facility: Investigational Site Number 840101
state: Tennessee
city: Fort Worth
country: United States
facility: Investigational Site Number 840323
state: Texas
city: Newport News
country: United States
facility: Investigational Site Number 840219
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840102
state: Virginia
city: Seattle
country: United States
facility: Investigational Site Number 840312
state: Washington
city: Tacoma
country: United States
facility: Investigational Site Number 840344
state: Washington
city: Morgantown
country: United States
facility: Investigational Site Number 840322
state: West Virginia
city: Wauwatosa
country: United States
facility: Investigational Site Number 840331
state: Wisconsin
city: Brugge
country: Belgium
facility: Investigational Site Number 056004
city: Brussel
country: Belgium
facility: Investigational Site Number 056003
city: Liège
country: Belgium
facility: Investigational Site Number 056001
city: Edmonton
country: Canada
facility: Investigational Site Number 124003
city: Greenfield Park
country: Canada
facility: Investigational Site Number 124006
city: London
country: Canada
facility: Investigational Site Number 124005
city: Oshawa
country: Canada
facility: Investigational Site Number 124007
city: Quebec
country: Canada
facility: Investigational Site Number 124004
city: Toronto
country: Canada
facility: Investigational Site Number 124001
city: Brest
country: France
facility: Investigational Site Number 250007
city: Dijon
country: France
facility: Investigational Site Number 250002
city: Limoges Cedex
country: France
facility: Investigational Site Number 250009
city: Marseille
country: France
facility: Investigational Site Number 250003
city: Paris Cedex 13
country: France
facility: Investigational Site Number 250004
city: Pierre Benite Cedex
country: France
facility: Investigational Site Number 250010
city: Poitiers
country: France
facility: Investigational Site Number 250008
city: Saint-Herblain Cedex
country: France
facility: Investigational Site Number 250001
city: Strasbourg
country: France
facility: Investigational Site Number 250006
city: Tours Cedex 1
country: France
facility: Investigational Site Number 250005
city: Amberg
country: Germany
facility: Investigational Site Number 276002
city: Berlin
country: Germany
facility: Investigational Site Number 276004
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 276007
city: Großhansdorf
country: Germany
facility: Investigational Site Number 276008
city: Halle/Saale
country: Germany
facility: Investigational Site Number 276010
city: Heidelberg
country: Germany
facility: Investigational Site Number 276012
city: Immenhausen
country: Germany
facility: Investigational Site Number 276009
city: Löwenstein
country: Germany
facility: Investigational Site Number 276001
city: München
country: Germany
facility: Investigational Site Number 276006
city: Oldenburg
country: Germany
facility: Investigational Site Number 276003
city: Budapest
country: Hungary
facility: Investigational Site Number 348005
city: Budapest
country: Hungary
facility: Investigational Site Number 348003
city: Mátraháza
country: Hungary
facility: Investigational Site Number 348001
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number 348004
city: Kfar Saba
country: Israel
facility: Investigational Site Number 376002
city: Petah-Tikva
country: Israel
facility: Investigational Site Number 376005
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376003
city: Tzrifin
country: Israel
facility: Investigational Site Number 376001
city: Genova
country: Italy
facility: Investigational Site Number 380006
city: Novara
country: Italy
facility: Investigational Site Number 380001
city: Orbassano
country: Italy
facility: Investigational Site Number 380008
city: Perugia
country: Italy
facility: Investigational Site Number 380002
city: Roma
country: Italy
facility: Investigational Site Number 380003
city: Roma
country: Italy
facility: Investigational Site Number 380007
city: Luxembourg
country: Luxembourg
facility: Investigational Site Number 442001
city: Breda
country: Netherlands
facility: Investigational Site Number 528005
city: Eindhoven
country: Netherlands
facility: Investigational Site Number 528004
city: Groningen
country: Netherlands
facility: Investigational Site Number 528001
city: Maastricht
country: Netherlands
facility: Investigational Site Number 528006
city: Zwolle
country: Netherlands
facility: Investigational Site Number 528003
city: Bialystok
country: Poland
facility: Investigational Site Number 616006
city: Krakow
country: Poland
facility: Investigational Site Number 616001
city: Lubin
country: Poland
facility: Investigational Site Number 616007
city: Olsztyn
country: Poland
facility: Investigational Site Number 616004
city: Torun
country: Poland
facility: Investigational Site Number 616008
city: Warszawa
country: Poland
facility: Investigational Site Number 616002
city: Wroclaw
country: Poland
facility: Investigational Site Number 616005
city: Alba Iulia
country: Romania
facility: Investigational Site Number 642002
city: Bucuresti
country: Romania
facility: Investigational Site Number 642006
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642001
city: Craiova
country: Romania
facility: Investigational Site Number 642004
city: Hunedoara
country: Romania
facility: Investigational Site Number 642005
city: Badalona
country: Spain
facility: Investigational Site Number 724009
city: Barcelona
country: Spain
facility: Investigational Site Number 724003
city: La Coruña
country: Spain
facility: Investigational Site Number 724004
city: Madrid
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724006
city: Málaga
country: Spain
facility: Investigational Site Number 724002
city: Palma De Mallorca
country: Spain
facility: Investigational Site Number 724001
city: Sevilla
country: Spain
facility: Investigational Site Number 724008
city: Valencia
country: Spain
facility: Investigational Site Number 724010
city: Zaragoza
country: Spain
facility: Investigational Site Number 724007
city: Glasgow
country: United Kingdom
facility: Investigational Site Number 826002
city: Leeds
country: United Kingdom
facility: Investigational Site Number 826005
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826001
city: Wolverhampton
country: United Kingdom
facility: Investigational Site Number 826006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: