Clinical Trials /

Safety Study of Afatinib for Brain Cancer

NCT02423525

Description:

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).

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligoastrocytoma
  • Anaplastic Oligodendroglioma
  • Brain metastasis
  • Chordoma
  • Glioblastoma
  • Glioma
  • Malignant Brain Neoplasm
  • Malignant Leptomeningeal Neoplasm
  • Medulloblastoma
  • Meningioma
  • Pituitary Gland Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of Afatinib for Brain Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1200.229
  • SECONDARY ID: 20161975
  • NCT ID: NCT02423525

Conditions

  • Brain Cancer

Interventions

DrugSynonymsArms
AfatinibGilotrifAfatinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
AfatinibExperimentalFour 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
  • Afatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis

               1. Dose Escalation Cohorts: 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

               2. Expansion Cohort: Histologically confirmed diagnosis of high-grade glioma with
                  altered EGFR (e.g., amplification, mutation), including:

                    1. glioblastoma (GBM),

                    2. anaplastic astrocytoma (AA),

                    3. anaplastic oligodendroglioma (AO),

                    4. 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:

               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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of dose limiting toxicities of pulsatile afatinib
Time Frame:first 28 days of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Treatment-emergent adverse events
Time Frame:7 months
Safety Issue:
Description:
Measure:Afatinib levels in cerebrospinal fluid (CSF) and blood
Time Frame:52 days
Safety Issue:
Description:
Measure:Objective response rate as assessed by the RANO criteria
Time Frame:approximately 6 months to 1 year
Safety Issue:
Description:
Measure:Best overall response rate
Time Frame:approximately 6 months to 1 year
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:up to 5 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Santosh Kesari

Trial Keywords

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

Last Updated

October 19, 2017