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Safety Study of Afatinib for Brain Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by John Wayne Cancer Institute
Boehringer Ingelheim
Information provided by (Responsible Party):
Santosh Kesari, John Wayne Cancer Institute Identifier:
First received: February 5, 2015
Last updated: March 3, 2017
Last verified: March 2017

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).

Condition Intervention Phase
Brain Cancer
Drug: Afatinib
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by John Wayne Cancer Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 24
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)
Arms Assigned Interventions
Experimental: Afatinib

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

Drug: Afatinib
Other Name: Gilotrif

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed diagnosis of brain cancer:

    1. glioblastoma (GBM),
    2. anaplastic astrocytoma (AA),
    3. anaplastic oligodendroglioma (AO),
    4. anaplastic mixed oligoastrocytoma (AMO),
    5. low grade gliomas,
    6. brain metastases,
    7. meningiomas,
    8. leptomeningeal metastases
    9. chordomas
    10. pituitary tumors
    11. medulloblastomas
  • Has failed prior standard therapy including maximal safe surgical resection (when appropriate for the specific cancer type), radiation therapy (when appropriate for the specific cancer type), and systemic therapy (when appropriate for the specific cancer type).
  • For diagnosis of GBM: has undergone maximal safe surgical resection, a course of postoperative radiation therapy with concurrent temozolomide, and maintenance temozolomide.
  • For diagnosis of meningioma: has no other option of standard therapy such as surgical resection (partial or total resection) or radiation.
  • Age 18 years and older.
  • Karnofsky Performance Status ≥ 60%.
  • Adequate organ function, defined as all of the following:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    2. Platelet count ≥ 100 x 109/L.
    3. Hemoglobin ≥ 9.0 g/dL.
    4. Total Bilirubin ≤ 1.5 institution's upper limit of normal (ULN).
    5. Aspartate amino transferase (AST) ≤ 2.5 x institution's ULN.
    6. Alanine amino transferase (ALT) ≤ 2.5 x institution's ULN.
    7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related.
  • Recovered from any previous therapy-related toxicity to Grade 1 or to their clinical baseline at study entry.
  • Women of child-bearing potential has negative serum or urine pregnancy test before the initiation of study drug dosing.

Exclusion Criteria:

  • Insufficient time from prior therapy to study entry:

    1. less than 28 days from whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS);
    2. less than 28 days from any investigational agent;
    3. less than 28 days from prior cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine (for GBM: 14 days from irinotecan or topotecan), 42 days from nitrosoureas, 21 days from procarbazine, irinotecan or topotecan administration);
    4. less than 14 days from hormonal treatment
    5. less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.
    6. When radiation necrosis is suspected, standard of care confirmatory imaging, such as MRI perfusion, magnetic resonance (MR) spectroscopy and or PET will be performed, and patients with findings consistent with radiation necrosis will be excluded.
  • Current or anticipated use of enzyme-inducing anti-epileptic drugs (EIAED).
  • Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
  • Known hypersensitivity to afatinib or its excipients.
  • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3 or 4, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months prior to enrollment.
  • Pregnant, nursing, or not using acceptable method of birth control.
  • Any history of or concomitant condition that would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.
  • Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
  • Known pre-existing interstitial lung disease.
  • Known active hepatitis B infection (defined as presence of Hep B sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
  • Prior participation in a blinded afatinib clinical study, even if not assigned to afatinib treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02423525

Contact: Najee Boucher 310-582-7460

United States, California
John Wayne Cancer Institute Recruiting
Santa Monica, California, United States, 90404
Contact: Najee Boucher    310-582-7340   
Principal Investigator: Santosh Kesari, MD, PhD         
Sponsors and Collaborators
Santosh Kesari
Boehringer Ingelheim
Principal Investigator: Santosh Kesari, MD, PhD John Wayne Cancer Institute
  More Information

Responsible Party: Santosh Kesari, Director, Neuro-Oncology, John Wayne Cancer Institute Identifier: NCT02423525     History of Changes
Other Study ID Numbers: 1200.229
20161975 ( Other Identifier: Western Institutional Review Board )
Study First Received: February 5, 2015
Last Updated: March 3, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by John Wayne Cancer Institute:
mixed oligoastrocytoma
low grade gliomas
brain metastases
leptomeningeal metastases

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases processed this record on April 28, 2017