Bevacizumab in Extensive Small Cell Lung Cancer

NCT ID: NCT00930891

Last Updated: 2016-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-07-31

Brief Summary

Despite the fact that a substantial response rate may be obtained in small-cell lung cancers (using double-drug chemotherapy: cisplatin-etoposide, PE), a cure remains an exception. More aggressive regimens remain controversial and recent attempts at increasing dose-intensity have been restricted to patients with a more favourable presentation.

Bevacizumab is a humanized monoclonal antibody which binds to VEGF (Vascular Endothelial Growth Factor). In association with double-drug standard chemotherapies, it has been proven that bevacizumab can improve survival of previously untreated advanced non-small-cell lung cancers (NSCLC), compared to chemotherapy without bevacizumab). Such promising effects on NSCLC deserve to be tested on small-cell lung cancers.

In this trial (IFCT-0802), standard chemotherapy (PCDE or PE) will be compared to experimental treatment (PCDE or PE + bevacizumab 7.5 mg/kg) for previously untreated SCLC patients.

Conditions

Small Cell Lung Cancer

Study Design

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

Study Groups

Arm A

4 additional cycles of chemotherapy

Group Type: ACTIVE_COMPARATOR

Standard Chemotherapy (PCDE or PE)

Intervention Type: DRUG

PCDE: cisPlatin 75 mg/m² D2 ; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 4 cycles

PE: cisPlatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 4 cycles

Prerandomization Chemotherapy (PCDE or PE)

Intervention Type: DRUG

PCDE: cisPlatin 75 mg/m² D2; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 2 cycles

PE: cisplatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 2 cycles

Arm B

4 additional cycles of chemotherapy + bevacizumab

Group Type: EXPERIMENTAL

Experimental Treatment (PCDE or PE + bevacizumab)

Intervention Type: DRUG

PCDE: cisPlatin 75 mg/m² D2; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 4 cycles Bevacizumab 7.5 mg/kg, D1, until progression

PE: cisPlatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 4 cycles Bevacizumab 7.5 mg/kg, D1, until progression

Prerandomization Chemotherapy (PCDE or PE)

Intervention Type: DRUG

PCDE: cisPlatin 75 mg/m² D2; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 2 cycles

PE: cisplatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 2 cycles

Interventions

Standard Chemotherapy (PCDE or PE)

PCDE: cisPlatin 75 mg/m² D2 ; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 4 cycles

PE: cisPlatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 4 cycles

Intervention Type: DRUG

Experimental Treatment (PCDE or PE + bevacizumab)

PCDE: cisPlatin 75 mg/m² D2; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 4 cycles Bevacizumab 7.5 mg/kg, D1, until progression

PE: cisPlatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 4 cycles Bevacizumab 7.5 mg/kg, D1, until progression

Intervention Type: DRUG

Prerandomization Chemotherapy (PCDE or PE)

PCDE: cisPlatin 75 mg/m² D2; Cyclophosphamide 300 mg/m² D1 to D3; 4'-epiDoxorubicin 30 mg/m² D1; Etoposide 75 mg/m² D1 to D3, 2 cycles

PE: cisplatin 80 mg/m², D2; Etoposide 120 mg/m² D1 to D3, 2 cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Small-Cell Lung Cancer histologically or cytologically proved
• Extended disease as defined by Veteran's Administration Lung Cancer Group (VALG)
• At least one unidimensionally measurable lesion (RECIST criterion)
• Age between 18 and 75 years
• Weight loss < 10% for the last three month
• Performance Status (PS)≤ 2
• Creatininemia < 110 µmol/L and creatinin clearance > 60 mL/min
• Neutrophils ≥ 1,500/µL and platelets ≥ 100,000/µL
• Bilirubin ≤ 1.5 x normal value
• Transaminases, Alkaline Phosphatase ≤ 2.5 x ULN excepted in case of liver metastasis (5xULN)
• Left ventricular ejection fraction (measured by echocardiographic or isotopic method) > 50% if PCDE is planned
• Electrocardiogram without uncontrolled coronaropathy
• Signed informed consent

Randomization Criteria (to be checked during the randomization (week 0)):

• Partial or complete tumoral response as defined by RECIST
• All chemotherapy-induced toxicities decreased to level ≤ 2 as defined by NCI CTC VS 3 (except for alopecia)

Exclusion Criteria

• Non-Small-Cell Lung Cancer or mixed cancer (small-cell / non-small-cell)
• Previous antitumoral treatment of the small-cell lung cancer (chemotherapy, radiotherapy, immunotherapy, surgery)
• Non-extended disease as defined by VALG
• Natremia < 125 mmol/L
• Hypercalcemia whereas a corrective treatment
• Pathology contra-indicating the hyper-hydration
• Hemoptysis in the last three months
• Tumor invading large vessels or invading the proximal trachea-bronchial tree (visible at the medical imagery). Investigator or radiologist must reject tumors adjoining, merging or extending to large vessel's lumen (for example : pulmonary artery, superior vena cava)
• Symptomatic cerebral or meningeal metastasis
• Other cancer in progress or medical history of cancer in the five last years (excepted basal cell carcinoma or in situ cervical cancer of the uterus.
• Important surgical intervention (including surgical biopsy), traumatic lesion during 28 days before starting the treatment, or anticipation of an important surgical intervention during the study
• Minor surgical intervention, including implanting permanent catheter during the 24 hours before the first administration of bevacizumab
• Unhealed wound, evolutive gastroduodenal ulcer, fractured bone
• Medical history of abdominal fistula, trachea-oesophageal fistula, of another type with a severity rank of 4, gastrointestinal perforation or intraabdominal abscess during 6 month before inclusion
• Ongoing or recent use of aspirin (during 10 days before the first administration of bevacizumab) (>325 mg/day) or use of another platelet aggregation inhibitor (dipyridamole, ticlopidine, clopidogrel > 75 mg/day), or ongoing or recent use of a therapeutic dose (during 10 days before the first administration of bevacizumab) of anticoagulant or thrombolytic drugs per os or in parenteral injection. Prophylactic use of anticoagulant drug is allowed
• Medical history or genetic predisposition to bleeding or coagulopathy
• Clinically significative cardiac disease: infarct or CVA during 6 month before inclusion, unstable angina, congestive cardiac failure level > II as defined by New York Heart Association (NYHA) or cardiac arrythmia needing a specific treatment which risk to interfere with the study, or uncontrolled arrythmia.
• Known allergy or hypersensibility to monoclonal antibodies (bevacizumab), to chinese hamster ovary cells or to any humanized or recombinant antibody
• Uncontrolled high blood pressure (systolic pressure > 150 mm Hg and/or diastolic pressure > 100 mm Hg), with or without hypotension treatment. Patients presenting an high blood pressure are eligibles if their treatment can decrease their blood pressure to the values required by the protocol.
• Severe ongoing infectious disease or fever > 38.5°C or evidence of any other pathology, organic or neurologic functions deterioration, physical examination or laboratory result which cause suspicion of a disease which contra-indicate use of any studied treatment.
• Woman with a positive pregnancy test or who has not made a pregnancy test (unless pregnancy risk can be excluded)
• Lactating woman
• Sexually active woman who don't use hormonal or mechanical contraceptive method or sexually active man who has a sexually active partner who don't want to use an effective contraceptive method during the course of the study and during the 6 months after last treatment administration
• Patient who as already been included and treated in the present study
• Patient who participate or who has participated in another study during 4 weeks before treatment administration
• Patient who receive a previous antiangiogenic treatment (experimental or commercial : bevacizumab, thalidomide, CP-547632, sunitinib, sorafenib...)
• Geographical or psychological condition which not allowed a good comprehension or compliance to protocol
• Liberty deprived patient

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intergroupe Francophone de Cancerologie Thoracique

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Louis PUJOL, Pr

Role: PRINCIPAL_INVESTIGATOR

CHRU Montpellier

Locations

Annemasse - CH

Ambilly, , France

Angers - CHU

Angers, , France

Armentières - CH

Armentières, , France

CHU Besancon - Pneumologie

Besançon, , France

Centre F. Baclesse

Caen, , France

CHU - Pneumologie

Caen, , France

Cahors - CH

Cahors, , France

Chauny - CH

Chauny, , France

Chalons-en-Champagne - CH

Châlons-en-Champagne, , France

Hôpital Percy-Armées - Pneumologie

Clamart, , France

Clermont Ferrand - CHU

Clermont-Ferrand, , France

Colmar - CH

Colmar, , France

CH - Compiègne

Compiègne, , France

Créteil - CHI

Créteil, , France

Dijon - CAC

Dijon, , France

Dijon - CHU

Dijon, , France

Draguignan - CH

Draguignan, , France

CHU Grenoble - pneumologie

Grenoble, , France

Harfleur - Clinique du Petit Colmoulins

Harfleur, , France

Saint Omer - CHI

Helfaut, , France

Jonzac - CH

Jonzac, , France

Chartres - CH

Le Coudray, , France

Centre Hospitalier - Pneumologie

Le Mans, , France

CH

Longjumeau, , France

APHM - Hôpital Sainte Marguerite

Marseille, , France

Marseille - CRLCC

Marseille, , France

Maubeuge - Polyclinique du Parc

Maubeuge, , France

Meaux - CH

Meaux, , France

Metz - CHR

Metz, , France

Mont de Marsan - CH

Mont-de-Marsan, , France

Montpellier - CHRU

Montpellier, , France

Mulhouse - CH

Mulhouse, , France

Neuilly - Hôpital Américain de Paris

Neuilly, , France

Nevers - CH

Nevers, , France

Nice - CAC

Nice, , France

Orléans - CH

Orléans, , France

APHP - Saint-Antoine - pneumologie

Paris, , France

APHP - Hopital Tenon - Pneumologie

Paris, , France

Pau - CH

Pau, , France

HCL - Lyon Sud (Pneumologie)

Pierre-Bénite, , France

Reims - CHU

Reims, , France

Reims - CRLCC

Reims, , France

Rouen - CHU

Rouen, , France

Saint Brieuc - CHG

Saint-Brieuc, , France

Saint Nazaire - Centre Etienne Dolet

Saint-Nazaire, , France

Saint Priest en Jarez - ICL

Saint-Priest-en-Jarez, , France

Saint Quentin - CH

Saint-Quentin, , France

Saverne - CH

Saverne, , France

Senlis - CH

Senlis, , France

Nouvel Hopital Civil - Pneumologie

Strasbourg, , France

Suresnes - Hopital Foch

Suresnes, , France

Thonon les bains

Thonon-les-Bains, , France

Toulon - HIA

Toulon, , France

CHU Toulouse - Pneumologie

Toulouse, , France

Toulouse - Clinique Pasteur

Toulouse, , France

Tours - CHU

Tours, , France

Nancy - CHU

Vandœuvre-lès-Nancy, , France

Verdun - CHG

Verdun, , France

Vesoul - CHI

Vesoul, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Geneve J, Maraninchi D. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007 Sep 1;25(25):3945-51. doi: 10.1200/JCO.2007.11.8109.

Reference Type: BACKGROUND

PMID: 17761978 (View on PubMed)

Pujol JL, Daures JP, Riviere A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarie E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. doi: 10.1093/jnci/93.4.300.

Reference Type: BACKGROUND

PMID: 11181777 (View on PubMed)

Horn L, Dahlberg SE, Sandler AB, Dowlati A, Moore DF, Murren JR, Schiller JH. Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. J Clin Oncol. 2009 Dec 10;27(35):6006-11. doi: 10.1200/JCO.2009.23.7545. Epub 2009 Oct 13.

Reference Type: BACKGROUND

PMID: 19826110 (View on PubMed)

Pujol JL, Lavole A, Quoix E, Molinier O, Souquet PJ, Barlesi F, Le Caer H, Moro-Sibilot D, Fournel P, Oster JP, Chatellain P, Barre P, Jeannin G, Mourlanette P, Derollez M, Herman D, Renault A, Dayen C, Lamy PJ, Langlais A, Morin F, Zalcman G; French Cooperative Thoracic Intergroup (IFCT). Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trialdagger. Ann Oncol. 2015 May;26(5):908-914. doi: 10.1093/annonc/mdv065. Epub 2015 Feb 16.

Reference Type: RESULT

PMID: 25688059 (View on PubMed)

Negre E, Coffy A, Langlais A, Daures JP, Lavole A, Quoix E, Molinier O, Greillier L, Audigier-Valette C, Moro-Sibilot D, Westeel V, Morin F, Roch B, Pujol JL. Development and Validation of a Simplified Prognostic Score in SCLC. JTO Clin Res Rep. 2020 Feb 12;1(1):100016. doi: 10.1016/j.jtocrr.2020.100016. eCollection 2020 Mar.

Reference Type: DERIVED

PMID: 34589918 (View on PubMed)

Related Links

http://www.ifct.fr

IFCT official website

Other Identifiers

2009-010187-42

Identifier Type: -

Identifier Source: secondary_id

IFCT-0802

Identifier Type: -

Identifier Source: org_study_id