Inoperable Non-Squamous NSCLC Stage III/IV: A Randomised Phase II Study With Bevacizumab Plus Erlotinib Or Gemcitabine/Cisplatin Plus Bevacizumab (INNOVATIONS)

This study has been completed.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Aktion Bronchialkarzinom e.V.
ClinicalTrials.gov Identifier:
NCT00536640
First received: September 27, 2007
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

This study wants to determine the activity of a non chemotherapy first line biological treatment with Erlotinib/Bevacizumab or Gemcitabine-Cisplatin/Bevacizumab in patients with the diagnosis of non-squamous advanced Non Small Lung Cancer.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Erlotinib
Drug: Bevacizumab
Drug: Gemcitabine
Drug: Cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Inoperable Non-Squamous NSCLC Stage III/IV: A Randomised Phase II Study With Bevacizumab Plus Erlotinib Or Gemcitabin/Cisplatin Plus Bevacizumab

Resource links provided by NLM:


Further study details as provided by Aktion Bronchialkarzinom e.V.:

Primary Outcome Measures:
  • The main efficacy parameter is the progression free survival. [ Time Frame: Recruitment 1 year, Follow up 2 years ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Recruitment 1 year, Follow up 2 years ]
  • Quality of life [ Time Frame: Screening, prior to next treatment cycle, treatment day 126, end of therapy ]
  • Response rate [ Time Frame: Screening, prior to treatment cycle 3, prior to treatment clycle 5, treatment day 126, every 6 weeks after treatment day 126, end of therapy ]
  • Molecular investigations [ Time Frame: Screening, prior to treatment cycle 3 ]

Enrollment: 224
Study Start Date: November 2007
Study Completion Date: May 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Erlotinib, Bevacizumab) Drug: Erlotinib
150 mg per os, given daily until tumor progression
Drug: Bevacizumab
15mg/kg i.v. on day 1 (three-week cycle) until tumor progression
Active Comparator: Arm B (Gemcitabine, Cisplatin, Bevacizumab) Drug: Bevacizumab
15mg/kg i.v. on day 1 (three-week cycle) until tumor progression
Drug: Gemcitabine
1250 mg/2 i.v. on day 1 and day 8 (three-week cycle) until tumor progression for a maximum of 6 cycles
Drug: Cisplatin
80 mg/m2 i.v. on day 1 (three-week cycle) until tumor progression for a maximum of 6 cycles. (The administration of 40 mg/2 Cisplatin on day 1 and day 8 is also possible)

Detailed Description:

Prospective, randomized multi-center, open label phase II study to determine the activity of a non-chemotherapy first line biological treatment with Erlotinib/Bevacizumab or Gemcitabine-Cisplatin/Bevacizumab in patients with the diagnosis of non-squamous advanced Non-Small-Lung-Cancer.

  • Duration of treatment/patient: up to 1,5 years
  • Follow Up: ≈ 6 month
  • Planned number of patients: 220 treated patients (110 patients/arm)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological confirmed Non-Small Cell Lung Cancer that can not be treated within a defined radiological field
  • Tumor stage IIIB (pleural effusion or pericardial effusion included) or IV
  • The following histological tumor types are eligible:

    • Adenocarcinoma (including adenocarcinomas with bronchioloalveolar differentiation)
    • Large Cell Carcinoma (including large cell carcinomas with neuroendocrine differentiation)
    • Mixed Cell Carcinoma without small cell fraction and without predominant squamous cell fraction (< 50%)
    • undifferentiated non-small-cell-carcinoma
  • No previous chemotherapy within the last five years
  • At least 4 weeks since last major surgery
  • Age ≥ 18 years
  • ECOG <= 2
  • Adequate hematological laboratory parameters

    • Hemoglobin ≥ 10 g/dl
    • WBC ≥ 3.000/µl
    • Platelets ≥ 100.000/µl
  • Adequate hepatic laboratory parameters

    • Bilirubin <= 2,0 mg/dl
    • AST(GOT) <= 2,5 x ULN in patients without liver metastases
    • AST(GOT) <= 5 x UNL in patients with liver metastases
    • ALT(GPT) <= 2,5 x ULN in patients without liver metastases
    • ALT(GPT) <= 5 x UNL in patients with liver metastases
  • Adequate renal laboratory parameters

    • Creatinine <= 1,5 mg/dl
    • Creatinine Clearance > 60 ml/min
  • Adequate plasmatic blood coagulation - INR <= 1,5 and PTT <= 1,5 x ULN
  • Normal cardiac function defined by LVEF > 49% (echocardiography)
  • Electrocardiogram without significant signs of cardiac arrhythmias
  • Provision of informed consent according to local regulatory requirements prior to any protocol specific treatment
  • Measurable lesion according to RECIST-Criteria's
  • Negative pregnancy test for women of childbearing potential unless they are postmenopausal at baseline. (Postmenopausal women must have been amenorrheic at least for 12 months to be considered of non childbearing potential)
  • Women of child bearing potential to must be willing to use an acceptable method to avoid pregnancy at least one month before study start. Examples: oral contraceptives (sole application of oral contraceptives is not sufficient), diaphragm pessary, intrauterine device (spiral), condom plus diaphragm pessary plus spermicide

Exclusion Criteria:

  • Histologic confirmed squamous cell carcinoma
  • Pregnancy or lactation period
  • Tumor extension treatable with radiotherapy
  • Current clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan
  • Evidence of tumor invading or abutting major blood vessels
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of a CIS of the cervix or non-melanomatous skin cancer. Patients curatively treated and free of disease for at least 5 years will be discussed with the Principal Investigator (LKP) before inclusion
  • Any previous chemotherapy within the last five years
  • Any radiotherapy with exception of the following situations:

    • concomitant small field radiotherapy in the case of solitary bone metastases or other solitary metastases
    • in case of large field radiotherapy or multi-radiation fields due to multiple bone metastases or other metastases. The application of study medication then must be delayed at least for 24 h (after last radiotherapy)
    • in case of radiotherapy of the primary tumor trial therapy can be employed if radiotherapy has ended at least 6 weeks ago and new tumor progression is clearly documented
  • Treatment with an investigational new drug, currently or within the last 28 days, and/or participation in another clinical trial, currently or during the last 12 weeks, and/or previous participation in this study
  • A history or presence of any CNS disorder or psychiatric disability judged by the Investigator to be clinically significant and/or interfering with compliance of oral drug intake
  • Patients with any clinically significant disease that in the opinion of the investigator is likely to put the patient at risk or to interfere with the evaluation of the patient's safety and of the study outcome. This includes, but is not limited to:

    • Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended)
    • Immediate need for therapeutic intervention (e.g.: upper inflow congestion or poststenotic pneumonia)
    • Clinically significant cardiac disease (e.g. right-sided heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months
    • pleural effusion or pericardial effusion with the need for intervention
  • Uncontrolled hypertension
  • Non healing wound, ulcer or bone fracture
  • Fresh thrombosis under therapy with anticoagulants
  • Hemorrhagic diathesis, Hemophilia A, Hemophilia B
  • Implantation of a central vein catheter (Prot-Catheter) within 24 h prior to application of study medication
  • Present hemoptysis of any CTC grade or history of hemoptysis of any CTC grade within 3 month prior to study start
  • Peritoneal carcinomatosis
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to study start
  • Interstitial pneumonia or extensive or symptomatic interstitial fibrosis of the lung
  • Pleural effusion or ascites, which cause respiratory compromise
  • Any other active or uncontrolled infection
  • Organ allograft
  • History of a mental disease or condition such as to interfere with the patient's ability to understand the requirements of the study and the intake of study medication according to study protocol
  • Inability to swallow pills
  • Current or recent (within 10 days of first dose of study medication) use of coumadin/warfarin or marcumar/phenprocoumon for therapeutic purposes Prophylactic use of low molecular weight heparins is allowed
  • Current or recent (within 10 days of first dose of study medication) use of ASS - Dosage > 325 mg/day
  • Current or recent (within 10 days of first dose of study medication) use of Plavix/Clopidogrel
  • Alcohol and drug abuse
  • Known hypersensitivity to any of the study drugs
  • Presence of a tracheobronchial fistula or fistulization in other organ systems like gastrointestinal fistulas or fistulization of urogenital tract
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00536640

Locations
Germany
Klinikum Bayreuth GmbH
Bayreuth, Germany, D-95445
Helios Klinikum Emil v. Behring
Berlin, Germany, D-14165
Gemeinschaftskrankenhaus Havelhöhe
Berlin, Germany, D-14089
Charite´ Mitte
Berlin, Germany, D-10117
Augusta-Krankenanstalten
Bochum, Germany, D-44791
Johanniter-Krankenhaus Bonn
Bonn, Germany, D-53113
Forschungszentrum Borstel
Borstel, Germany, D-23845
St. Johannes Hospital
Duisburg, Germany, D-47166
Städtisches Krankenhaus Frankfurt-Höchst
Frankfurt, Germany, D-65929
Krankenhaus Nordwest
Frankfurt am Main, Germany, D-60488
Klinikum Frankfurt (Oder)GmbH
Frankfurt Oder, Germany, D-15232
Medizinisches Versorgungszentrum Osthessen
Fulda, Germany, D-36043
Universitätsklinikum Greifswald
Greifswald, Germany, D-17487
Krankenhaus Großhansdorf
Großhansdorf, Germany, D-22927
Georg-August-Universität Göttingen
Göttingen, Germany, D-37075
Diakoniekrankenhaus Halle/S.
Halle, Germany, D-06114
Asklepios Klinik Harburg
Hamburg, Germany, D-21075
Thoraxklinik Universitätsklinikum Heidelberg
Heidelberg, Germany, D-69126
Lungenklinik Hemer
Hemer, Germany, 58675
Fachklinik für Lungenerkrankungen Immenhausen
Immenhausen, Germany, D-34376
St. Vincentius-Kliniken Karlsruhe
Karlsruhe, Germany, D-76137
Klinikum Kassel GmbH
Kassel, Germany, 34125
Katholisches Klinikum Haus Marienhof
Koblenz, Germany, 56073
Malteser Krankenhaus St. Hildegardis
Köln, Germany, D-50931
Onkologische Schwerpunktpraxis Dr. Lothar Müller
Leer, Germany, D-26789
Klinikum Lippe-Lemgo
Lemgo, Germany, D-32657
Klinikum Ludwigshafen
Ludwigshafen, Germany, D-67063
Klinik Löwenstein
Löwenstein, Germany, 74245
Universitätsklinikum Schleswig-Holstein
Lübeck, Germany, D-23538
St. Hildegardis Krankenhaus
Mainz, Germany, D-55131
Universitätsklinikum Marburg
Marburg, Germany, D-35033
Johannes Wesling Klinikum Minden
Minden, Germany, 32429
Krankenhaus Barmherzige Brüder
Regensburg, Germany, D-93049
Hanse-Klinikum Stralsund
Stralsund, Germany, D-18410
Onkologische Gemeinschaftspraxis Dr. Nusch
Velbert, Germany, D-42551
Fachkliniken Wangen
Wangen, Germany, D-88239
Helios Klinikum Wuppertal
Wuppertal, Germany, D-42283
Sponsors and Collaborators
Aktion Bronchialkarzinom e.V.
Roche Pharma AG
Investigators
Principal Investigator: Prof. Dr. Martin Wolf, MD Aktion Bronchialkarzinom e.V.
  More Information

No publications provided

Responsible Party: Aktion Bronchialkarzinom e.V.
ClinicalTrials.gov Identifier: NCT00536640     History of Changes
Other Study ID Numbers: ABC-2006-NSCLC-01, 2006-004865-32
Study First Received: September 27, 2007
Last Updated: June 11, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Aktion Bronchialkarzinom e.V.:
Non Small Cell Lung Carcinoma (NSCLC Stage III an IV)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Bevacizumab
Cisplatin
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 22, 2014