Bevacizumab and Erlotinib in Lung Cancer With Brain Metastases, a Phase II Trial

NCT02655536 | Unknown Phase 2

• 1 other identifier: 201510073MIPB
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, multicenter phase II study conducting in 3 medical centers in Asia. Patients will receive erlotinib in combination with bevacizumab or erlotinib alone. This study will enroll EGFR-mutant NSCLC patients who have asymptomatic brain metastases. The primary objective is to compare the systemic progression-free survival (PFS) to bevacizumab plus erlotinib versus erlotinib alone in patients with EGFR mutant NSCLC who have asymptomatic brain metastases.

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The PFS will be evaluated from date of randomization until the date of documented progression or the date of death from any cause, whichever came first.

  The PFS will be evaluated per RECIST 1.1 criteria every 6 weeks for the first 12 months and then every 12 weeks up to 36 months.

Secondary Outcomes (7)

• overall survival

  The survival will be assessed from date of randomization until the date of death from any cause. The survival will be assessed every 3 weeks up to 36 months.

• overall response rate

  The response rate will be evaluated per RECIST 1.1 criteria every 6 weeks for the first 12 months and then every 12 weeks up to 36 months.

• Time-to-central nervous system (CNS) progression

  Time-to-central nervous system(CNS) progression will be evaluated per RECIST 1.1 criteria every 6 weeks for the first 12 months and then every 12 weeks up to 36 months.

• Time to extra-CNS progression

  Time to extra-CNS progression will be evaluated per RECIST 1.1 criteria every 6 weeks for the first 12 months and then every 12 weeks up to 36 months.

• The PFS-2 in patients in patients with CNS progression only

  The PFS-2 will be evaluated per RECIST 1.1 criteria every 6 weeks for the first 12 months and then every 12 weeks up to 36 months.

Study Arms (2)

bevacizumab plus erlotinib

EXPERIMENTAL

bevacizumab 15mg/kg every 3 weeks plus erlotinib 150mg per day

Drug: Bevacizumab plus erlotinib

erlotinib

ACTIVE COMPARATOR

erlotinib 150mg per day

Drug: Erlotinib

Interventions

Bevacizumab plus erlotinib DRUG

Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of every 3 weeks cycle by IV infusion erlotinib will be give at 150mg orally every day for 21 days of every 3 weeks cycle

Also known as: avastin plus tarceva

bevacizumab plus erlotinib

Erlotinib DRUG

erlotinib will be give at 150mg orally every day for 21 days of every 3 weeks cycle

Also known as: tarceva

erlotinib

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed, stage IV (AJCC 7th Edition) non-small cell lung cancer.
• A tumor harboring an EGFR mutation known to be associated with erlotinib sensitivity (exon 19 deletion and L858R)
• Documented brain metastases.
• At least one measure brain lesion and one extracranial lesion
• No emergent operation or radiotherapy is indicated. Patients who have received operation for brain tumor may be enrolled if they have recovered from the operation and there are measurable brain lesions after operation.
• No prior exposure to EGFR inhibitors or anti-angiogenesis therapy including bevacizumab.
• No prior systemic anti-cancer therapy for advanced NSCLC is allowed. -Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the start of study treatment.
• Written informed consent obtained prior to any screening procedures.
• ≥20 years of age.
• Must have discontinued any previous anti-cancer and investigational therapy for at least 28 days, major operation for at least 28 days with full healing of surgical wounds, or radiotherapy for at least 14 days before study treatment administration, and must have recovered to grade 1 from the adverse effects of such treatment before starting study treatment.
• Life expectancy ≥ 3 months.
• ECOG performance status: 0-1.
• Female patients of child-bearing potential should have a negative pregnancy test.
• Required baseline laboratory status:
• Hemoglobin\>9g/dL Platelet count≥100x109/L Absolute neutrophil count (ANC)≥1.5x109/L without growth factor support Total bilirubin\>1.5x upper limit of normal (ULN) AST/SGOT and/or ALT/SGPT\>2.5x ULN Serum creatinine clearance \>50 ml/min, by either Cockcroft-Gault formula or by 24-hour urine collection analysis

You may not qualify if:

• Squamous cell carcinoma
• Unable or unwilling to swallow tablet once daily.
• allergy to erlotinib and/or bevacizumab
• Previous treatment of EGFR inhibitors or anti-angiogenesis therapies.
• History of gross hemoptysis (defined as bright red blood of at least 1/2 teaspoon or 2.5 mL per episode) within 3 months prior to randomization unless definitively treated with surgery or radiation
• Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control the CNS condition.
• CNS bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months
• Chronic daily use of aspirin (\>325 mg/day) or other full-dose NSAIDs with anti platelet activity. Treatment with other antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, and/or cilostazol) is permitted.
• Other baseline laboratory values Uncontrolled hypercalcemia (\>11.5 mg/dL) Urinary protein to creatinine ratio \>1 (spot urine) Serum creatinine \>2.0 ULN
• Radiation therapy within 2 weeks prior to the first dose of study drug. Any persistent side effect of prior radiotherapy must be resolved to grade 1 prior to the first dose of study treatment.
• Any unresolved toxicity from previous anticancer therapy \> Grade 1.
• Currently receiving any prohibited medications including vitamins supplements, and herbal supplements.
• Unable to undergo an MRI or contrast CT procedures.
• Active HBV or HCV infection, HBV carrier can be enrolled if HBV DNA titer is low under antiviral treatment.
• Known history of HIV seropositivity. HIV testing is not required as part of this study.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Oncology, Nationa Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Related Publications (1)

• Deng Z, Qin Y, Liu Y, Zhang Y, Lu Y. Role of Antiangiogenic Agents Combined With EGFR Tyrosine Kinase Inhibitors in Treatment-naive Lung Cancer: A Meta-Analysis. Clin Lung Cancer. 2021 Jan;22(1):e70-e83. doi: 10.1016/j.cllc.2020.08.005. Epub 2020 Sep 18.

  PMID: 33067126 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: January 14, 2016
• Study Start: August 1, 2017
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

TW (1)