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Bevacizumab and Erlotinib Followed by Cisplatin or Carboplatin and Gemcitabine in Treating Patients With Newly Diagnosed or Recurrent Stage IIIB or Stage IV NSCLC

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ClinicalTrials.gov Identifier: NCT00354549
Recruitment Status : Completed
First Posted : July 20, 2006
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief Summary:

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, carboplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with erlotinib followed by cisplatin or carboplatin and gemcitabine at disease progression may be an effective treatment for non-small cell lung cancer.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib followed by cisplatin or carboplatin and gemcitabine works in treating patients with newly diagnosed or recurrent stage IIIB or stage IV non-small cell lung cancer.


Condition or disease Intervention/treatment Phase
Lung Cancer Drug: bevacizumab + erlotinib hydrochloride Drug: gemcitabine hydrochloride + cisplatin or carboplatin Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Assess the efficacy of bevacizumab and erlotinib hydrochloride as initial therapy in patients with newly diagnosed or recurrent stage IIIB or IV non-squamous non-small cell lung cancer (NSCLC).

Secondary

  • Assess the safety of bevacizumab and erlotinib hydrochloride as initial therapy in these patients.
  • Assess the quality of life (QOL) in patients treated with bevacizumab and erlotinib hydrochloride.
  • Assess the efficacy and safety of subsequent cisplatin or carboplatin in combination with gemcitabine hydrochloride in patients who have disease progression.
  • Assess the QOL in patients treated with subsequent cisplatin or carboplatin in combination with gemcitabine hydrochloride at disease progression.

Tertiary

  • Identify novel biomarkers in predicting response to therapy and toxicity in patients treated with bevacizumab and erlotinib hydrochloride as initial therapy.

OUTLINE: This is a multicenter, prospective, open-label study.

Patients receive bevacizumab IV over 90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Beginning within 3 weeks of documented disease progression, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. They also receive cisplatin IV over 1 hour or carboplatin IV over 30 minutes on day 1. Treatment with gemcitabine hydrochloride with either cisplatin or carboplatin repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and periodically during study treatment.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 101 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bevacizumab and Erlotinib First-Line Therapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (Stage IIIB/IV) Followed by Platinum-Based Chemotherapy at Disease Progression. A Multicenter Phase II Trial
Study Start Date : January 2006
Actual Primary Completion Date : April 2009
Actual Study Completion Date : September 2010



Intervention Details:
  • Drug: bevacizumab + erlotinib hydrochloride
    Patients receive bevacizumab IV over 90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Drug: gemcitabine hydrochloride + cisplatin or carboplatin
    Beginning within 3 weeks of documented disease progression, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. They also receive cisplatin IV over 1 hour or carboplatin IV over 30 minutes on day 1. Treatment with gemcitabine hydrochloride with either cisplatin or carboplatin repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.


Primary Outcome Measures :
  1. Disease stabilization (DS) (complete response [CR], partial response [PR], or stable disease [SD]) as assessed by RECIST criteria after 12 weeks of treatment with bevacizumab and erlotinib hydrochloride [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. DS as assessed by RECIST criteria after 6 and 18 weeks of treatment with bevacizumab and erlotinib hydrochloride [ Time Frame: 6 and 18 weeks ]
  2. Objective response (CR or PR) as assessed by RECIST criteria after 6, 12, and 18 weeks of treatment with bevacizumab and erlotinib hydrochloride [ Time Frame: 6, 12 and 18 weeks ]
  3. Best overall response when treated with bevacizumab and erlotinib hydrochloride [ Time Frame: Until treatment ends ]
  4. Adverse events (AEs) when treated with bevacizumab and erlotinib hydrochloride [ Time Frame: Until treatment ends ]
  5. Time to progression (TTP) when treated with bevacizumab and erlotinib hydrochloride [ Time Frame: Until treatment ends ]
  6. Time to treatment failure (TTF) when treated with bevacizumab and erlotinib hydrochloride [ Time Frame: Until treatment ends ]
  7. Quality of life (QOL) when treated with bevacizumab and erlotinib hydrochloride [ Time Frame: Until treatment ends ]
  8. Objective response (CR or PR) when treated with chemotherapy [ Time Frame: Until treatment ends ]
  9. Unexpected adverse drug reaction [ Time Frame: Until treatment ends ]
  10. QOL when treated with chemotherapy [ Time Frame: Periodically ]
  11. Overall survival (OS) in patients treated with bevacizumab and erlotinib hydrochloride and in patients treated with subsequent chemotherapy at disease progression [ Time Frame: life-long ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC)

    • Newly diagnosed or recurrent disease
  • Meets 1 of the following staging criteria:

    • Stage IIIB disease, meeting both of the following criteria:

      • Proven malignant effusion or supraclavicular node involvement (i.e., N3 supraclavicular nodes)
      • Not a candidate for curative multimodality treatment or surgery
    • Stage IV disease
  • Measurable disease, defined as ≥ 1 lesion (outside of irradiated areas) that can be measured in ≥ 1 dimension as ≥ 10 mm by spiral or multi-slice CT scan or MRI
  • Immediate chemotherapy not clinically mandatory in the judgement of the investigator
  • No intrathoracic large, centrally located tumors and/or cavitary lesions invading or abutting major blood vessels
  • No evidence of clinically active interstitial lung disease

    • Patients with chronic stable radiographic changes who are asymptomatic are eligible
  • No small cell lung cancer (SCLC), squamous NSCLC, or combined SCLC-NSCLC tumors
  • No brain metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Hemoglobin ≥ 10 g/dL
  • Absolute neutrophil count ≥ 1,500/mm³
  • Thrombocyte count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN (5 times ULN if liver metastases present)
  • Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present)
  • Quick ≥ 70% OR INR ≤ 1.5
  • Creatinine ≤ 2.0 times ULN
  • Proteinuria ≤ 2+ by urine dipstick
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study treatment
  • Able to understand trial information given by the investigator and complete quality of life questionnaire
  • No pre-existing condition that would preclude swallowing and/or absorption of oral medication
  • No prior or concurrent malignancies, except for the following:

    • Malignancy for which the minimum relapse-free interval is ≥ 5 years
    • Nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
  • No other medical condition that would preclude study participation, including any of the following:

    • Unstable or uncompensated respiratory, cardiac, hepatic, or renal disease
    • Active infection
    • Uncontrolled diabetes mellitus
    • Hypertension ≥ 150/100 mm Hg despite treatment
    • Myocardial infarction within the past 3 months
    • History of hemorrhagic disorders
    • Non-healing wound, ulcer, or bone fracture
  • No clinical history of coagulopathy or thrombosis
  • No hemoptysis or hematemesis ≥ grade 2 (defined as bright red blood of ≥ 5 mL per episode) within the past 6 months
  • No known hypersensitivity to study drug(s) or to any other component of the study drugs
  • No significant traumatic injury within the past 28 days
  • No serious underlying medical condition that would impair the ability of the patient to participate in the trial or that would preclude use of study drugs
  • No cerebrovascular accident or other CNS bleeding within the past 6 months

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior radiotherapy and recovered

    • No prior radiotherapy to lesion(s) selected for measurement
  • No prior chemotherapy for advanced disease

    • At least 6 months since prior neoadjuvant or adjuvant systemic chemotherapy for NSCLC
    • Prior intrapleural or intrapericardial local chemotherapy allowed
  • No prior endothelial growth factor and/or vascular endothelial growth factor (receptor)-targeted therapy for NSCLC
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 30 days since prior treatment in another clinical trial
  • No concurrent anticoagulants (e.g., phenprocoumon, acenocoumarol, or full-dose warfarin or heparin)
  • No concurrent full-dose continuous use of non-steroid anti-inflammatory drugs (NSAIDs)
  • No concurrent aspirin or clopidogrel bisulfate

    • Low-dose aspirin (≤ 325 mg daily) may be continued in patients at high risk for arterial thromboembolic disease
  • No other concurrent drugs contraindicated for use with the study drugs, according to the Swissmedic-approved product information
  • No other concurrent experimental drugs or anticancer therapy, including chemotherapy, immunotherapy, or hormone therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00354549


Locations
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Switzerland
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, CH-6500
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
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Study Chair: Francesco Zappa, MD Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Publications of Results:

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Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00354549    
Other Study ID Numbers: SAKK 19/05
EU-20614
First Posted: July 20, 2006    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Keywords provided by Swiss Group for Clinical Cancer Research:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Bevacizumab
Carboplatin
Erlotinib Hydrochloride
Antineoplastic Agents
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Protein Kinase Inhibitors