Bevacizumab in Extensive Small Cell Lung Cancer (CPC)

March 9, 2016 updated by: Intergroupe Francophone de Cancerologie Thoracique

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

143

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: 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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate (complete response + partial response)
Time Frame: 6 weeks after randomization
6 weeks after randomization

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 12 weeks
12 weeks
Complete response length
Time Frame: 12 weeks
12 weeks
Quality of life
Time Frame: 12 weeks
12 weeks
Toxicities
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intergroupe Francophone de Cancerologie Thoracique

Investigators

  • Principal Investigator: Jean-Louis PUJOL, Pr, CHRU Montpellier

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

July 1, 2009

First Submitted That Met QC Criteria

July 1, 2009

First Posted (Estimate)

July 2, 2009

Study Record Updates

Last Update Posted (Estimate)

March 10, 2016

Last Update Submitted That Met QC Criteria

March 9, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFCT-0802
  • 2009-010187-42

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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