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

NCT ID: NCT00354549

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2010-09-30

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.

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Zappa, MD

Role: STUDY_CHAIR

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Locations

Universitaetsspital-Basel

Basel, , Switzerland

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Countries

Switzerland

References

Zappa F, Droege C, Betticher D, von Moos R, Bubendorf L, Ochsenbein A, Gautschi O, Oppliger Leibundgut E, Froesch P, Stahel R, Hess T, Rauch D, Schmid P, Mayer M, Crowe S, Brauchli P, Ribi K, Pless M; Swiss Group for Clinical Cancer Research (SAKK). Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: a multicenter phase II trial (SAKK 19/05). Lung Cancer. 2012 Dec;78(3):239-44. doi: 10.1016/j.lungcan.2012.08.017. Epub 2012 Sep 23.

Reference Type: RESULT

PMID: 23009726 (View on PubMed)

Baty F, Joerger M, Fruh M, Klingbiel D, Zappa F, Brutsche M. 24h-gene variation effect of combined bevacizumab/erlotinib in advanced non-squamous non-small cell lung cancer using exon array blood profiling. J Transl Med. 2017 Mar 30;15(1):66. doi: 10.1186/s12967-017-1174-z.

Reference Type: RESULT

PMID: 28359318 (View on PubMed)

Franzini A, Baty F, Macovei II, Durr O, Droege C, Betticher D, Grigoriu BD, Klingbiel D, Zappa F, Brutsche MH. Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non-Small Cell Lung Cancer Patients (SAKK 19/05 trial). Clin Cancer Res. 2015 Dec 1;21(23):5253-63. doi: 10.1158/1078-0432.CCR-14-3135. Epub 2015 Apr 28.

Reference Type: RESULT

PMID: 25922429 (View on PubMed)

Joerger M, Baty F, Fruh M, Droege C, Stahel RA, Betticher DC, von Moos R, Ochsenbein A, Pless M, Gautschi O, Rothschild S, Brauchli P, Klingbiel D, Zappa F, Brutsche M. Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05). Lung Cancer. 2014 Aug;85(2):306-13. doi: 10.1016/j.lungcan.2014.04.014. Epub 2014 May 29.

Reference Type: RESULT

PMID: 24928469 (View on PubMed)

Other Identifiers

EU-20614

Identifier Type: -

Identifier Source: secondary_id

SAKK 19/05

Identifier Type: -

Identifier Source: org_study_id