Safety Study of Afatinib for Brain Cancer
The purpose of this study is to try to determine the maximum safe dose of afatinib that can be administered to people with brain cancer. Other purposes of this study are to:
- find out what effects (good and bad) afatinib has;
- see how much drug gets into the body by collecting blood and cerebrospinal fluid for use in pharmacokinetic (PK) studies;
- learn more about how afatinib might affect the growth of cancer cells;
- look at biomarkers (biochemical features that can be used to measure the progress of disease or the effects of a drug).
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation and Central Nervous System (CNS) Pharmacokinetic Study of the ErbB Family Inhibitor Afatinib in Patients With Recurrent or Progressive Brain Cancer|
- Rate of dose limiting toxicities of pulsatile afatinib [ Time Frame: first 28 days of treatment ]
- Maximum tolerated dose (MTD) of pulsatile afatinib [ Time Frame: first 28 days of treatment ]
- Treatment-emergent adverse events [ Time Frame: 7 months ]
- Afatinib levels in cerebrospinal fluid (CSF) and blood [ Time Frame: 52 days ]
- Objective response rate as assessed by the RANO criteria [ Time Frame: approximately 6 months to 1 year ]
- Best overall response rate [ Time Frame: approximately 6 months to 1 year ]
- Progression free survival [ Time Frame: up to 5 years ]
- Overall Survival [ Time Frame: up to 5 years ]
|Actual Study Start Date:||December 2016|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||December 2019 (Final data collection date for primary outcome measure)|
Four dosing cohorts are planned, with the option to enroll additional cohorts based on safety and PK data. Afatinib tablets are taken by mouth every 4 days.
Dose Level 1: 80 mg Dose Level 2: 120 mg Dose Level 3: 180 mg Dose Level 4: 200 mg
Other Name: Gilotrif
This is an open-label, single institution, Phase I 3+3 dose escalation study to describe the safety and tolerability of afatinib in patients with brain cancer having failed prior therapy and to determine the recommended phase II dose.
Eligible patients will receive afatinib in treatment cycles of 28 days that will consist of afatinib administered orally by mouth once every four days. Patients will be assigned to the dose level open at the time of their enrollment. Patients will continue dosing of afatinib until disease progression, unacceptable toxicity, withdrawal of consent, or treating physician determines it is in their best interest to stop. Guidelines for modifying study drug doses is provided for the management of adverse treatment effects.
All patients will have regular evaluations for assessment of safety parameters as detailed in the study flow chart. Lumbar puncture and blood draw for assessing afatinib levels will occur as detailed in the study flow chart.
Neurological imaging and assessment for response will be performed approximately every eight weeks. Tumor response will be assessed according to Response Assessment in Neuro-Oncology (RANO) Working Group criteria.
An end of treatment evaluation will occur when a patient permanently discontinues study drug, as detailed in the study flow chart. Patients will then be followed every four months for survival.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02423525
|Contact: Najee Boucher||310-582-7460||Najee.Boucher@providence.org|
|United States, California|
|John Wayne Cancer Institute||Recruiting|
|Santa Monica, California, United States, 90404|
|Contact: Najee Boucher 310-582-7340 Najee.Boucher@providence.org|
|Principal Investigator: Santosh Kesari, MD, PhD|
|Principal Investigator:||Santosh Kesari, MD, PhD||John Wayne Cancer Institute|