Comparator-Controlled Study for EGFR(+) Patients With Multiple BMs From NSCLC (BROKE) (EGFR-epidermal Growth Factor Receptor;BM-brain Metastases)

NCT02338011 | Unknown Phase 2 DMC

• 1 other identifier: ShanghaiChest Hospital
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM.
2. 2.Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM.
3. 3.Explore the rescuable therapy after progression of disease.

Conditions

Non-Small Cell Lung Cancer; Brain Metastases; EGFR Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Time to progression

  Compare the progression free survival(PFS) and safety in two arms,including intracranial PFS、extracranial PFS and overall PFS.

  12-14 months

Secondary Outcomes (4)

• Overall survival

  3 years

• Disease Progression Classification

  3 years

• Health-related quality of life

  3 years

• Mental Status

  3 years

Study Arms (2)

Gefitinib alone

EXPERIMENTAL

Patients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib 250mg per day until progression of disease.

Drug: Gefitinib

Gefitinib concurrent WBRT

EXPERIMENTAL

Patients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib concurrent WBRT until progression of disease.Gefitinib was given 250mg per day. WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions).

Drug: Gefitinib; Radiation: WBRT

Interventions

Gefitinib DRUG

Gefitinib was given 250mg per day. Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed.

Also known as: Iressa

Gefitinib alone; Gefitinib concurrent WBRT

WBRT RADIATION

WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions).

Gefitinib concurrent WBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• ECOG score ≤ 2
• Recursive Partitioning Analysis(RPA) Class I-II;
• The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs;
• Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations;
• Enhanced MRI showed brain metastases ≥ 4;
• or 2 line treatment revealed failure;
• No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously；
• No treatment for BM previously,including WBRT、SRS、surgery or experimental therapy;
• Expected survival period over 3 months;
• Two weeks before randomization, organs function in patients with meet the following criteria:
• bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L;
• liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal;
• renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min;
• Urine dipstick testing the proteinuria \< 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must \< 500mg;

You may not qualify if:

• Patients have been treated with brain radiation or surgery of BM;
• Prior of EGFR-TKIs；
• Mixed with small cell lung cancer patients with components;
• Wild-type of EGFR;
• Unable to tolerate MRI scanning;
• Post 2 line treated patients;
• Brain meninges metastases or incorporate with brain meninges metastases;
• years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor);
• Before entering the group 4 weeks received any other investigational drugs;
• Incorporate with local symptoms（hemiplegic paralysis、anepia、nystagmus、ataxia.et);
• Pregnancy or lactation female;
• Allergic to EGFR-TKIs or any components;
• Patients were not permitted to receive the following drugs: phenytoin, carbamazepine, rifampicin, phenobarbital or itraconazole because of their potential to affect the metabolism of EGFR-TKIs and reduce its plasma concentration. Patients were not permitted to receive oral medicine such as CoumadinTM、Warfarin. If anticoagulant therapy is needed,low molecular heparin is suggested to instead of Coumarin drugs;
• Organs function in patients with meet the following criteria:
• Diagnose with interstitial lung disease、drug induced interstitial disease、hormone dependent radiation pneumonia previously,et al;

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Varian linear accelerato

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Gefitinib

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Liyan JIang, M.D,Ph.D.

  Department of Respiratory, Shanghai Chest Hospital,Shanghai JIaotong University

  STUDY DIRECTOR

Central Study Contacts

Liyan JIang, M.D,Ph.D.

CONTACT

18017321302; liyanjiangxkyy@sina.cn

Xiaolong FU, M.D,Ph.D.

CONTACT

13651635103; xlfu1964@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Respiratory, Shanghai Chest Hospital

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: January 14, 2015
• Study Start: November 1, 2014
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: January 26, 2015

Record last verified: 2015-01

Locations

CN (1)