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)

Squamous Cell Lung Cancer Clinical Trial

— ECLIPSE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01082549
• Other study ID #: EFC11553
• Secondary ID: 20090321
• Status: Completed
• Phase: Phase 3
• First received: March 5, 2010
• Last updated: February 17, 2016
• Start date: March 2010
• Est. completion date: April 2013

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 780
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Squamous Cell Lung Cancer

Intervention

Drug:
• gemcitabine/carboplatin
i.v.
• gemcitabine/carboplatin plus Iniparib
i.v.

Locations

Country	Name	City	State
Belgium	Investigational Site Number 056004	Brugge
Belgium	Investigational Site Number 056003	Brussel
Belgium	Investigational Site Number 056001	Liège
Canada	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 124001	Toronto
France	Investigational Site Number 250007	Brest
France	Investigational Site Number 250002	Dijon
France	Investigational Site Number 250009	Limoges Cedex
France	Investigational Site Number 250003	Marseille
France	Investigational Site Number 250004	Paris Cedex 13
France	Investigational Site Number 250010	Pierre Benite Cedex
France	Investigational Site Number 250008	Poitiers
France	Investigational Site Number 250001	Saint-Herblain Cedex
France	Investigational Site Number 250006	Strasbourg
France	Investigational Site Number 250005	Tours Cedex 1
Germany	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/Saale
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
Hungary	Investigational Site Number 348003	Budapest
Hungary	Investigational Site Number 348005	Budapest
Hungary	Investigational Site Number 348001	Mátraháza
Hungary	Investigational Site Number 348004	Nyíregyháza
Israel	Investigational Site Number 376002	Kfar Saba
Israel	Investigational Site Number 376005	Petah-Tikva
Israel	Investigational Site Number 376003	Tel Hashomer
Israel	Investigational Site Number 376001	Tzrifin
Italy	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
Luxembourg	Investigational Site Number 442001	Luxembourg
Netherlands	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
Poland	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	Warszawa
Poland	Investigational Site Number 616005	Wroclaw
Romania	Investigational Site Number 642002	Alba Iulia
Romania	Investigational Site Number 642006	Bucuresti
Romania	Investigational Site Number 642001	Cluj Napoca
Romania	Investigational Site Number 642004	Craiova
Romania	Investigational Site Number 642005	Hunedoara
Spain	Investigational Site Number 724009	Badalona
Spain	Investigational Site Number 724003	Barcelona
Spain	Investigational Site Number 724004	La Coruña
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	Sevilla
Spain	Investigational Site Number 724010	Valencia
Spain	Investigational Site Number 724007	Zaragoza
United Kingdom	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 States	Investigational Site Number 840338	Anaheim	California
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 840311	Bend	Oregon
United States	Investigational Site Number 840202	Bethesda	Maryland
United States	Investigational Site Number 840306	Birmingham	Alabama
United States	Investigational Site Number 840210	Bridgeton	Missouri
United States	Investigational Site Number 840353	Burbank	California
United States	Investigational Site Number 840350	Chapel Hill	North Carolina
United States	Investigational Site Number 840352	Charleston	South Carolina
United States	Investigational Site Number 840103	Chattanooga	Tennessee
United States	Investigational Site Number 840208	Chattanooga	Tennessee
United States	Investigational Site Number 840313	Chicago	Illinois
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 840203	Collierville	Tennessee
United States	Investigational Site Number 840106	Columbia	South Carolina
United States	Investigational Site Number 840335	Columbus	Ohio
United States	Investigational Site Number 840341	Concord	California
United States	Investigational Site Number 840336	Denver	Colorado
United States	Investigational Site Number 840317	Duarte	California
United States	Investigational Site Number 840330	Durham	North Carolina
United States	Investigational Site Number 840218	Evansville	Indiana
United States	Investigational Site Number 840323	Fort Worth	Texas
United States	Investigational Site Number 840216	Ft. Lauderdale	Florida
United States	Investigational Site Number 840201	Gainesville	Georgia
United States	Investigational Site Number 840207	Huntsville	Alabama
United States	Investigational Site Number 840319	Indianapolis	Indiana
United States	Investigational Site Number 840215	Jacksonville	Florida
United States	Investigational Site Number 840339	La Verne	California
United States	Investigational Site Number 840217	Lakeland	Florida
United States	Investigational Site Number 840318	Las Vegas	Nevada
United States	Investigational Site Number 840301	Lawrenceville	Georgia
United States	Investigational Site Number 840309	Loma Linda	California
United States	Investigational Site Number 840307	Los Angeles	California
United States	Investigational Site Number 840320	Louisville	Kentucky
United States	Investigational Site Number 840305	Marietta	Georgia
United States	Investigational Site Number 840327	Maywood	California
United States	Investigational Site Number 840322	Morgantown	West Virginia
United States	Investigational Site Number 840204	Morristown	New Jersey
United States	Investigational Site Number 840351	Muscle Shoals	Alabama
United States	Investigational Site Number 840101	Nashville	Tennessee
United States	Investigational Site Number 840315	Newark	Delaware
United States	Investigational Site Number 840219	Newport News	Virginia
United States	Investigational Site Number 840346	Norwich	Connecticut
United States	Investigational Site Number 840212	Omaha	Nebraska
United States	Investigational Site Number 840205	Orlando	Florida
United States	Investigational Site Number 840102	Richmond	Virginia
United States	Investigational Site Number 840337	Royal Oak	Michigan
United States	Investigational Site Number 840345	Salisbury	Maryland
United States	Investigational Site Number 840303	San Diego	California
United States	Investigational Site Number 840321	Santa Rosa	California
United States	Investigational Site Number 840104	Sarasota	Florida
United States	Investigational Site Number 840308	Scarborough	Maine
United States	Investigational Site Number 840312	Seattle	Washington
United States	Investigational Site Number 840329	South Bend	Indiana
United States	Investigational Site Number 840220	Spartanburg	South Carolina
United States	Investigational Site Number 840328	St. Louis Park	Minnesota
United States	Investigational Site Number 840326	Stockton	California
United States	Investigational Site Number 840344	Tacoma	Washington
United States	Investigational Site Number 840314	Tucker	Georgia
United States	Investigational Site Number 840310	Vallejo	California
United States	Investigational Site Number 840331	Wauwatosa	Wisconsin
United States	Investigational Site Number 840211	West Reading	Pennsylvania
United States	Investigational Site Number 840316	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		12 months, 24 months	No
Secondary	progression free survival		12 months	No