Safety Study of Afatinib for Brain Cancer

NCT02423525 | Completed Phase 1 FDA Drug

• 2 other identifiers: 1200.22920161975
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Brain Cancer

Keywords

glioblastoma; astrocytoma; oligodendroglioma; mixed oligoastrocytoma; low grade gliomas; brain metastases; meningiomas; leptomeningeal metastases

Outcome Measures

Primary Outcomes (2)

• Rate of dose limiting toxicities of pulsatile afatinib

  Number of side effects of study treatment that prevent an increase in dose or level of that treatment

  first 28 days of treatment

• Maximum tolerated dose (MTD) of pulsatile afatinib

  The highest dose evaluated that does not cause unacceptable side effects

  first 28 days of treatment

Secondary Outcomes (6)

• Treatment-emergent adverse events

  7 months

• Afatinib levels in cerebrospinal fluid (CSF) and blood

  52 days

• Objective response rate as assessed by the RANO criteria

  approximately 6 months to 1 year

• Best overall response rate

  approximately 6 months to 1 year

• Progression free survival

  up to 5 years

Study Arms (1)

Afatinib

EXPERIMENTAL

Afatinib tablets are taken by mouth. Dose Level 1: 80 mg every 4 days Dose Level 2: 120 mg every 4 days Dose Level 3: 180 mg every 4 days Dose Level 4: 280 mg every 7 days

Drug: Afatinib

Interventions

Afatinib DRUG

Also known as: Gilotrif

Afatinib

Eligibility Criteria

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

You may qualify if:

• Diagnosis
• Dose Escalation Cohorts: Histologically confirmed diagnosis of brain cancer:
• glioblastoma (GBM),
• anaplastic astrocytoma (AA),
• anaplastic oligodendroglioma (AO),
• anaplastic mixed oligoastrocytoma (AMO),
• low grade gliomas,
• brain metastases,
• meningiomas,
• leptomeningeal metastases
• chordomas
• pituitary tumors
• medulloblastomas
• Expansion Cohort: Histologically confirmed diagnosis of high-grade glioma with altered EGFR (e.g., amplification, mutation), including:
• glioblastoma (GBM),

You may not qualify if:

• Insufficient time from prior therapy to study entry:
• less than 28 days from whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS);
• less than 28 days from any investigational agent;
• 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);
• less than 14 days from hormonal treatment
• less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.
• 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.

Sponsors & Collaborators

• Santosh Kesari: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Astrocytoma; Oligodendroglioma; Meningioma; Meningeal Carcinomatosis

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Santosh Kesari, MD, PhD

  Saint John's 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: Director, Neuro-Oncology

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: April 22, 2015
• Study Start: December 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2021
• Last Updated: March 10, 2022

Record last verified: 2022-03

Locations

US (1)