Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Bevacizumab in Extensive Small Cell Lung Cancer (CPC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier:
NCT00930891
First received: July 1, 2009
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Small Cell Lung Cancer
Drug: Standard Chemotherapy (PCDE or PE)
Drug: Experimental Treatment (PCDE or PE + bevacizumab)
Drug: Prerandomization Chemotherapy (PCDE or PE)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Intergroupe Francophone de Cancerologie Thoracique:

Primary Outcome Measures:
  • Response rate (complete response + partial response) [ Time Frame: 6 weeks after randomization ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Complete response length [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Toxicities [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 143
Study Start Date: September 2009
Study Completion Date: July 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
4 additional cycles of chemotherapy
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

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

Experimental: Arm B
4 additional cycles of chemotherapy + bevacizumab
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

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


  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930891

  Hide Study Locations
Locations
France
Annemasse - CH
Ambilly, France, 74100
Angers - CHU
Angers, France, 49000
Armentières - CH
Armentières, France
CHU Besancon - Pneumologie
Besancon, France, 25000
Centre F. Baclesse
Caen, France, 14000
CHU - Pneumologie
Caen, France, 14000
Cahors - CH
Cahors, France, 46000
Chalons-en-Champagne - CH
Chalons-en-Champagne, France
Chauny - CH
Chauny, France
Hôpital Percy-Armées - Pneumologie
Clamart, France, 92140
Clermont Ferrand - CHU
Clermont Ferrand, France, 63000
Colmar - CH
Colmar, France, 68000
CH - Compiègne
Compiègne, France, 60300
Créteil - CHI
Créteil, France, 94000
Dijon - CAC
Dijon, France, 21000
Dijon - CHU
Dijon, France, 63000
Draguignan - CH
Draguignan, France, 83300
CHU Grenoble - pneumologie
Grenoble, France, 38000
Harfleur - Clinique du Petit Colmoulins
Harfleur, France, 76700
Saint Omer - CHI
Helfaut, France, 62570
Jonzac - CH
Jonzac, France, 17500
Chartres - CH
Le Coudray, France, 28630
Centre Hospitalier - Pneumologie
Le Mans, France, 72000
CH
Longjumeau, France
APHM - Hôpital Sainte Marguerite
Marseille, France, 13000
Marseille - CRLCC
Marseille, France
Maubeuge - Polyclinique du Parc
Maubeuge, France, 59600
Meaux - CH
Meaux, France, 77100
Metz - CHR
Metz, France, 57000
Mont de Marsan - CH
Mont de Marsan, France, 40000
Montpellier - CHRU
Montpellier, France, 34295
Mulhouse - CH
Mulhouse, France, 68000
Neuilly - Hôpital Américain de Paris
Neuilly, France, 92200
Nevers - CH
Nevers, France, 58033
Nice - CAC
Nice, France, 06000
Orléans - CH
Orléans, France, 45000
APHP - Hopital Tenon - Pneumologie
Paris, France, 75020
APHP - Saint-Antoine - pneumologie
Paris, France, 75012
Pau - CH
Pau, France, 64046
HCL - Lyon Sud (Pneumologie)
Pierre Bénite, France, 69495
Reims - CRLCC
Reims, France
Reims - CHU
Reims, France, 51092
Rouen - CHU
Rouen, France, 76000
Saint Brieuc - CHG
Saint Brieuc, France, 22000
Saint Nazaire - Centre Etienne Dolet
Saint Nazaire, France, 44600
Saint Priest en Jarez - ICL
Saint Priest en Jarez, France, 42270
Saint Quentin - CH
Saint Quentin, France, 02100
Saverne - CH
Saverne, France
Senlis - CH
Senlis, France, 60300
Nouvel Hopital Civil - Pneumologie
Strasbourg, France, 63000
Suresnes - Hopital Foch
Suresnes, France, 92151
Thonon les bains
Thonon les bains, France, 74200
Toulon - HIA
Toulon, France, 83000
CHU Toulouse - Pneumologie
Toulouse, France
Toulouse - Clinique Pasteur
Toulouse, France
Tours - CHU
Tours, France, 37000
Nancy - CHU
Vandoeuvre lès Nancy, France, 54500
Verdun - CHG
Verdun, France
Vesoul - CHI
Vesoul, France, 70000
Institut Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique
Investigators
Principal Investigator: Jean-Louis PUJOL, Pr CHRU Montpellier
  More Information

Additional Information:
Publications:
Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier: NCT00930891     History of Changes
Other Study ID Numbers: IFCT-0802, 2009-010187-42
Study First Received: July 1, 2009
Last Updated: October 24, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Intergroupe Francophone de Cancerologie Thoracique:
Extensive-Disease Small-Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bevacizumab
Cyclophosphamide
Epirubicin
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014