A phase II study of erlotinib and bevacizumab in patients with locally advanced and/or metastatic (stage IIIB or IV) non-small cell lung cancer who have not received prior chemotherapy

ISRCTN	ISRCTN78329606
DOI	https://doi.org/10.1186/ISRCTN78329606
Secondary identifying numbers	NTR528

Submission date: 20/02/2007
Registration date: 20/02/2007
Last edited: 26/03/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof H J M Groen
Scientific

University Medical Centre Groningen (UMCG)
Department of Pulmonary Disease
PO Box 30001
Groningen
9700 RB
Netherlands

Phone	+31 (0)50 361 6161
Email	h.j.m.groen@int.umcg.nl

Study information

Study design	An open label, multicentre, phase II study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	A phase II study of erlotinib and bevacizumab in patients with locally advanced and/or metastatic (stage IIIB or IV) non-small cell lung cancer who have not received prior chemotherapy
Study objectives	Tumour response from erlotinib and bevacizumab as first line treatment in advanced Non-Small Cell Lung Cancer (NSCLC) will result in non-progressive disease within six weeks in more than 50% of patients.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Non Small Cell Lung Cancer (NSCLC)
Intervention	All patients will receive: 1. Erlotinib 150 mg/day orally 2. Bevacizumab 15 mg/kg every three weeks as a 90 minutes infusion
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Erlotinib and bevacizumab
Primary outcome measure	Efficacy of erlotinib and bevacizumab in first line treatment of NSCLC as determined by the rate of no progression at six weeks.
Secondary outcome measures	Efficacy of erlotinib and bevacizumab as determined by: 1. The objective response rate 2. Duration of response 3. Time to disease progression or death 4. Survival 5. Safety of erlotinib and bevacizumab
Overall study start date	01/01/2006
Completion date	01/01/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	46
Total final enrolment	47
Key inclusion criteria	1. Cytologically or histologically advanced non-squamous NSCLC. Patients with squamous cell histology are eligible only if their intrathoracic disease has been completely resected, they have no current evidence of intrathoracic disease (with the exception of isolated pleural effusion), and they have not had haemoptysis in the 28 days prior to randomisation 2. No prior chemotherapy or therapy with systemic anti-tumor therapy (e.g., monoclonal antibody therapy) or prior exposure to agents directed at the Human Epidermal growth factor Receptor (HER) axis (e.g. Epidermal Growth Factor Receptor Tyrosine Kinase [EGFR TK] inhibitors, Herceptin). Prior surgery and/or localised irradiation is permitted provided that the irradiated lesion is not the only measurable lesion 3. Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria 4. Age 18 or greater 5. Eastern Cooperative Oncology Group (ECOG) performance status of zero to two 6. Life expectancy of at least 12 weeks 7. At least four weeks since any prior surgery or radiotherapy. Patients who, in the opinion of the investigator, have fully recovered from surgery in less than four weeks may also be considered for the study. Patients must have recovered (Common Toxicity Criteria [CTC] less than or equal to one) from acute toxicities of any previous therapy 8. Neutrophils more than or equal to 1.5 x 10^9/L and platelets more than 100 x 10^9/L 9. Serum bilirubin less than or equal to 1.5 x Upper Limit of Normal (ULN). Aspartate aminotransferase (ASAT)/Alanine aminotransferase (ALAT) less than or equal to 2.5 x ULN (in case of liver metastases less than or equal to 5 x ULN), Alkaline phosphatase less than or equal to 2.5 x ULN 10. Serum creatinine less than or equal to 1.5 x ULN or creatinine clearance more than or equal to 60 ml/min 11. Urine dipstick for proteinuria less than 2+. Patients discovered to have more than or equal to 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate less than or equal to 1 g of protein/24hr 12. Normal serum calcium 13. Able to comply with study and follow-up procedures 14. Able to take oral medication 15. For all females of childbearing potential a negative pregnancy test must be obtained within 48 hours before registration starting therapy 16. Patients with reproductive potential must use effective contraception 17. Written informed consent
Key exclusion criteria	1. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease) 2. Evidence of tumour invading major blood vessels 3. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day zero (patients must have recovered from any major surgery), or anticipation of need for major surgical procedure during the course of the study 4. Planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed) 5. Serious non-healing wound or ulcer 6. Evidence of bleeding diathesis or coagulopathy. Presence of a cavitary lesion or evidence of tumor invading or abutting major blood vessels 7. Brain metastasis or spinal cord compression that is newly diagnosed and/or has not yet been treated with surgery and/or radiation; previously diagnosed and treated Central Nervous System (CNS) metastases or spinal cord compression with evidence of stable disease for at least two months is permitted 8. Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease 9. History of haemorrhagic disorders 10. Current or recent (within ten days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling Intravenous (IV) catheters 11. History of more than or equal to grade two haemoptysis (symptomatic and medical intervention indicated) 12. Ongoing treatment with aspirin (more than 325 mg/day) or other medications known to predispose to gastrointestinal ulceration 13. Nursing mothers
Date of first enrolment	01/01/2006
Date of final enrolment	01/01/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Centre Groningen (UMCG)

Groningen
9700 RB
Netherlands

Sponsor information

University Medical Centre Groningen (UMCG) (The Netherlands)
University/education

PO Box 30001
Groningen
9700 RB
Netherlands

Website	http://www.umcg.nl/azg/nl/english/azg/
"ROR"	https://ror.org/03cv38k47

Funders

Funder type

Industry

Roche
Government organisation / For-profit companies (industry)

Alternative name(s): F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
Location: Switzerland

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/03/2011	26/03/2021	Yes	No

Editorial Notes

26/03/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.