Brain CancerPhase 1NCT02423525
Safety Study of Afatinib for Brain Cancer
A Phase 1 study testing Afatinib in people with Brain Cancer, run by Santosh Kesari at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Cancer
- What is being tested?
- Afatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2016to Aug 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis
- Dose Escalation Cohorts: Histologically confirmed diagnosis of brain cancer:
- glioblastoma (GBM),
- anaplastic astrocytoma (AA),
- anaplastic oligodendroglioma (AO),
- anaplastic mixed oligoastrocytoma (AMO),
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- 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),
- anaplastic astrocytoma (AA),
- anaplastic oligodendroglioma (AO),
- anaplastic mixed oligoastrocytoma (AMO)
- 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:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
- Platelet count ≥ 100 x 109/L.
- Hemoglobin ≥ 9.0 g/dL.
- Total Bilirubin ≤ 1.5 institution's upper limit of normal (ULN).
- Aspartate amino transferase (AST) ≤ 2.5 x institution's ULN.
- Alanine amino transferase (ALT) ≤ 2.5 x institution's ULN.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
John Wayne Cancer Institute
Santa Monica, California, 90404
About this study
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
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).
Read the 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.
- Conditions
- Brain Cancer
- Being tested
- Afatinib
- Keywords
- glioblastoma, astrocytoma, oligodendroglioma, mixed oligoastrocytoma, low grade gliomas, brain metastases, meningiomas, leptomeningeal metastases
- Medical subject headings
- Brain Neoplasms, Glioblastoma, Astrocytoma, Oligodendroglioma, Meningioma, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called Gilotrif
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: first 28 days of treatment
Maximum tolerated dose (MTD) of pulsatile afatinib
The highest dose evaluated that does not cause unacceptable side effects
Measured: first 28 days of treatment
Secondary outcomes (6)
Treatment-emergent adverse events
Type, number, grade and seriousness of adverse events reported after the first dose of study treatment
Measured: 7 months
Afatinib levels in cerebrospinal fluid (CSF) and blood
Measurement of afatinib concentration in CSF and blood at defined timepoints
Measured: 52 days
Objective response rate as assessed by the RANO criteria
Tumor response compared to baseline as assessed by the RANO criteria
Measured: approximately 6 months to 1 year
Best overall response rate
Best tumor response compared to baseline
Measured: approximately 6 months to 1 year
Progression free survival
Time between the start of treatment to disease progression
Measured: up to 5 years
Overall Survival
Time between the start of treatment to death
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startDec 2016
- Primary completionAug 2020
- Study completionAug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Santosh Kesari
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor-investigator, Santosh Kesari, Saint John's Cancer Institute
- Investigators
- Santosh Kesari, MD, PhD, Principal investigator, Saint John's Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423525
- Sponsor's protocol ID
- 1200.229
- Other IDs
- 20161975
- Status last verified
- Mar 2022
- First submitted
- 5 Feb 2015
- Last updated
- 10 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02423525
- Acronym / sponsor ID
- 1200.229
- Conditions
- Brain Cancer
- Keywords
- glioblastoma, astrocytoma, oligodendroglioma, mixed oligoastrocytoma, low grade gliomas, brain metastases, meningiomas, leptomeningeal metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Santosh KesariUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- Dec 2016 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2021 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afatinib | Experimental | Drug: AfatinibAfatinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Diagnosis
- 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.
Key exclusion criteria (17 listed)
- Insufficient time from prior therapy to study entry:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfatinibAlso: Gilotrif | Drug | Afatinib |
Primary outcome
Rate of dose limiting toxicities of pulsatile afatinib
Time frame: first 28 days of treatment
Number of side effects of study treatment that prevent an increase in dose or level of that treatment
Maximum tolerated dose (MTD) of pulsatile afatinib
Time frame: first 28 days of treatment
The highest dose evaluated that does not cause unacceptable side effects
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Santosh Kesari, MD, PhD principal investigator
Saint John's Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Afatinib in people with Brain Cancer, run by Santosh Kesari at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of dose limiting toxicities of pulsatile afatinib (time frame: first 28 days of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2022.