High Dose Gefitinib for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations

NCT00372515 | Completed Phase 1 DMC

• 1 other identifier: 05-403
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purposes of this study are to find out if using high doses of the drug Gefitinib (Iressa) as a way to treat patients with non-small cell lung cancer that has spread to the covering of the brain and/or spinal cord (meninges) results in any bad side effects; and to determine the highest dose that can be given to patients in this setting.

Conditions

Non-Small Cell Lung Cancer

Keywords

epidermal growth factor; EGFR; lung cancer; Iressa; Gefitinib

Outcome Measures

Primary Outcomes (1)

• To assess the safety of administering gefitinib in doses of 750mg to 1250mg in adult patients with carcinomatous meningitis from non-small cell lung cancer with known or suspected somatic EGFR mutations.

  2 years

Secondary Outcomes (3)

• To measure the cytologic response rate, response duration, time to neurologic progression, and survival following high dose gefitinib therapy administered on this schedule

  2 years

• to measure gefitinib levels with serum and cerebrospinal fluid while on therapy, and to correlate these levels with toxicity, response and survival

  2 years

• to examine archived tumors for the presence or absence of EGFR mutations and resistance mutations, and to correlate those mutations with cytologic response, time to neurologic progression, and survival.

  2 years

Study Arms (1)

High dose gefitinib

EXPERIMENTAL

Drug: Gefitinib

Interventions

Gefitinib DRUG

On days 1-14 gefitinib will be taken orally daily at either 750, 1000, or 1250mg (depends upon when subject entered trial). If medication is tolerated well, subject will take 500mg daily on days 15-28 of each 28-day cycle. Cycles (higher dose followed by lower dose) will be repeated as long as subject's cancer does not worsen and they do not experience any serious side effects.

Also known as: Iressa

High dose gefitinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven diagnosis of non-small cell lung cancer of any histologic subtype
• High likelihood of gefitinib sensitivity, as evidenced by one or more of the following: previous complete or partial response to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor, erlotinib, or gefitinib; known somatic mutation of the EGFR tyrosine kinase
• Recurrent or persistent disease as manifested by carcinomatous meningitis
• ECOG PS 0-3
• Age 18 years or older
• Greater than 2 weeks since prior radiation therapy
• Greater than 3 weeks since prior major surgery
• Adequate hematologic, renal, and/or hepatic function
• Coagulation parameters: international normalized ratio(INR)less than or equal to 1.5 and an activated thromboplastin time \< 50 seconds

You may not qualify if:

• Previous Grade 4 toxicity on gefitinib or erlotinib leading to dose reduction or interruption
• Uncontrolled brain metastases, or brain metastases associated with mass effect that would contraindicate lumbar puncture
• Any other malignancy within the past five years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin
• Dysphagia
• Active gastrointestinal disease or disorder that alters gastrointestinal motility or absorption
• Incomplete healing from previous oncologic or other major surgery
• Any pre-existing severe or unstable medical condition
• Any condition requiring concurrent and ongoing use of anticoagulation
• Inability to undergo collection of CSF, either by repeated lumbar puncture or placement of an Omaya reservoir
• Pregnant or breastfeeding
• Concurrent intrathecal drug administration or radiotherapy
• Concurrent systemic chemotherapy or investigational agent
• Anticoagulant except aspirin or heparin flushes
• Enzyme-inducing anti-epileptic drug
• CYP3A4 inhibitors

Sponsors & Collaborators

• David M. Jackman, MD: lead
• AstraZeneca: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Jackman DM, Cioffredi LA, Jacobs L, Sharmeen F, Morse LK, Lucca J, Plotkin SR, Marcoux PJ, Rabin MS, Lynch TJ, Johnson BE, Kesari S. A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer. Oncotarget. 2015 Feb 28;6(6):4527-36. doi: 10.18632/oncotarget.2886.

  PMID: 25784657 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Bruce Johnson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2006
• First Posted: September 7, 2006
• Study Start: June 1, 2006
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2015
• Last Updated: January 31, 2018

Record last verified: 2018-01

Locations

US (2)