Bevacizumab in Extensive Small Cell Lung Cancer

Small Cell Lung Cancer Clinical Trial

— CPC  

Official title:

Randomized Phase II-III Study of Bevacizumab 7,5 mg/kg in Combination With Chemotherapy Versus Chemotherapy in Extensive-Disease Small-Cell Lung Cancer After Response to Chemotherapy : PCDE (cisPlatin - Cyclophosphamide - epiDoxorubicin - Etoposide) or PE (cisPlatin - Etoposide)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00930891
• Other study ID #: IFCT-0802
• Secondary ID: 2009-010187-42
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 1, 2009
• Last updated: March 9, 2016
• Start date: September 2009
• Est. completion date: July 2013

Study information

• Verified date: March 2016
• Source: Intergroupe Francophone de Cancerologie Thoracique
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: July 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria (must be checked at the inclusion, week -8):

• 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)

• Inclusion criteria concerning creatininemia, clearance, neutrophils, platelets, transaminases, alkaline phosphatases and left ventricular ejection fraction must be checked again

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

Study Design

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• 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
• 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
• 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

Locations

Country	Name	City	State
France	Annemasse - CH	Ambilly
France	Angers - CHU	Angers
France	Armentières - CH	Armentières
France	CHU Besancon - Pneumologie	Besancon
France	Centre F. Baclesse	Caen
France	CHU - Pneumologie	Caen
France	Cahors - CH	Cahors
France	Chalons-en-Champagne - CH	Chalons-en-Champagne
France	Chauny - CH	Chauny
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 - Hopital Tenon - Pneumologie	Paris
France	APHP - Saint-Antoine - 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	Vandoeuvre lès Nancy
France	Verdun - CHG	Verdun
France	Vesoul - CHI	Vesoul
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone de Cancerologie Thoracique

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View Citation

Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Genève 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. — View Citation

Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié 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. — View Citation

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 Coop — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (complete response + partial response)		6 weeks after randomization	Yes
Secondary	Progression-free survival		12 weeks	Yes
Secondary	Complete response length		12 weeks	Yes
Secondary	Quality of life		12 weeks	No
Secondary	Toxicities		12 weeks	Yes

External Links

•   IFCT official website