Bevacizumab and Erlotinib Followed by Cisplatin or Carboplatin and Gemcitabine in Treating Patients With Newly Diagnosed or Recurrent Stage IIIB or Stage IV Non-Small Cell Lung Cancer - Full Text View

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00354549

Purpose

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	Intervention	Phase
Lung Cancer	Drug: bevacizumab Drug: carboplatin Drug: cisplatin Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Procedure: quality-of-life assessment	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Cisplatin Gemcitabine hydrochloride Gemcitabine Erlotinib Erlotinib hydrochloride Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 [ Designated as safety issue: No ]

Secondary Outcome Measures:

DS as assessed by RECIST criteria after 6 and 18 weeks of treatment with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Objective response (CR or PR) as assessed by RECIST criteria after 6, 12, and 18 weeks of treatment with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Best overall response when treated with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Adverse events (AEs) when treated with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: Yes ]
Time to progression (TTP) when treated with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Time to treatment failure (TTF) when treated with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Quality of life (QOL) when treated with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Patients receiving chemotherapy comprising cisplatin or carboplatin in combination with gemcitabine hydrochloride [ Designated as safety issue: No ]
DS when treated with chemotherapy [ Designated as safety issue: No ]
Objective response (CR or PR) when treated with chemotherapy [ Designated as safety issue: No ]
Unexpected adverse drug reaction [ Designated as safety issue: Yes ]
TTP when treated with chemotherapy [ Designated as safety issue: No ]
TTF when treated with chemotherapy [ Designated as safety issue: No ]
QOL when treated with chemotherapy [ Designated as safety issue: No ]
Overall survival (OS) in patients treated with bevacizumab and erlotinib hydrochloride and in patients treated with subsequent chemotherapy at disease progression [ Designated as safety issue: No ]
Correlate gene expression profile with response to treatment with bevacizumab and erlotinib hydrochloride [ Designated as safety issue: No ]
Correlate gene expression with TTP [ Designated as safety issue: No ]
Identification of genetic markers in the tumor tissue and serum predictive for toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	101
Study Start Date:	January 2006
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354549

Locations

Switzerland
Oncology Institute of Southern Switzerland	Recruiting
Bellinzona, Switzerland, CH-6500
Contact: Francesco Zappa, MD 41-91-811-4576
Universitaetsspital-Basel	Recruiting
Basel, Switzerland, CH-4031
Contact: Cornelia Droege, MD 41-61-265-5075 cdroege@uhbs.ch

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:

Francesco Zappa, MD

Oncology Institute of Southern Switzerland

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000495159, SWS-SAKK-19/05, EU-20614
Study First Received:	July 19, 2006
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00354549
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Erlotinib
Thoracic Neoplasms
Non-small cell lung cancer
Adenocarcinoma, Bronchiolo-Alveolar
Disease Progression
Carboplatin
Bevacizumab
Recurrence
Carcinoma

Adenocarcinoma of lung
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Gemcitabine
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors

Protein Kinase Inhibitors
Angiogenesis Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 14, 2009