Clinical Trials /

Pilot Study of Cabozantinib for Recurrent or Progressive High-Grade Glioma in Children

NCT02885324

Description:

This pilot will study the feasibility and exploratory efficacy of using Cabozantinib for recurrent or refractory high grade glioma for which there are no curative options. Patients will also be followed for safety, time to progression, event free survival and overall survival

Related Conditions:
  • Anaplastic Astrocytoma
  • Glioblastoma
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Cabozantinib for Recurrent or Progressive High-Grade Glioma in Children
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: IUSCC-0601
  • NCT ID: NCT02885324

Conditions

  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma

Interventions

DrugSynonymsArms
CabozantinibXL 184, CabometyxCabozantinib

Purpose

This pilot will study the feasibility and exploratory efficacy of using Cabozantinib for recurrent or refractory high grade glioma for which there are no curative options. Patients will also be followed for safety, time to progression, event free survival and overall survival

Trial Arms

NameTypeDescriptionInterventions
CabozantinibExperimentalCabozantininb will be taken daily at a dose of 40 mg/m2. Drug cycles will last 28 days and be continuous for up to 12 months of therapy on study.
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

          1. Age: Patients must be ≥ 2 years and ≤ 21 years of age

          2. Diagnosis: Patients with relapsed or refractory high grade glioma (HGG) defined was
             histologically confirmed WHO grade III or WHO grade IV glioma (i.e., glioblastoma
             multiforme or anaplastic astrocytoma). Patients must have had histologic verification
             of malignancy at original diagnosis or relapse. Metastatic disease to the spine is
             eligible. Patients may be in first, second, or third relapse. Subjects with intrinsic
             brain stem gliomas may be eligible if histologically confirmed. Please contact study
             chair prior to enrollment.

          3. Disease Status: Patients must have measurable disease. Linear enhancement of
             leptomeningeal without measurable mass is excluded.

          4. Therapeutic Options: Patient's current disease state must be one for which there is
             no known curative therapy or therapy proven to prolong survival with an acceptable
             quality of life.

          5. Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for
             patients ≤ 16 years of age. Note: Neurologic deficits in patients must have been
             relatively stable for at least 7 days prior to study enrollment. Patients who are
             unable to walk because of paralysis, but who are in a wheelchair, will be considered
             ambulatory for the purpose of assessing the performance score.

          6. Subjects must have a reasonable life expectancy of at least 2 months.

          7. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all
             prior anti-cancer chemotherapy

               1. Myelosuppressive chemotherapy: At least 21 days after the last dose of
                  myelosuppressive chemotherapy (42 days if prior nitrosourea).

               2. Hematopoietic growth factors: At least 14 days after the last dose of a
                  long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
                  factor. For agents that have known adverse events occurring beyond 7 days after
                  administration, this period must be extended beyond the time during which
                  adverse events are known to occur. The duration of this interval must be
                  discussed with the study chair.

               3. Biologic (anti-neoplastic agent): At least 7 days after the last dose of a
                  biologic agent. For agents that have known adverse events occurring beyond 7
                  days after administration, this period must be extended beyond the time during
                  which adverse events are known to occur. The duration of this interval must be
                  discussed with the study chair.

               4. Immunotherapy: At least 42 days after the completion of any type of
                  immunotherapy (e.g., tumor vaccines).

               5. Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose
                  of a monoclonal antibody.

               6. XRT: At least 14 days after local palliative XRT (small port); at least 150 days
                  must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of
                  pelvis; at least 42 days must have elapsed if other substantial BM radiation
                  (e.g., stem cell Infusion without TBI and no evidence of active graft vs. host
                  disease and at least 56 days must have elapsed after transplant or stem cell
                  infusion).

          8. Organ Function Requirements:

               1. Adequate bone marrow function defined as: Absolute neutrophil count (ANC
                  ≥1000/mm3)

               2. Platelet count ≥ 100,000/ mm3 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 7 days prior to enrollment)

               3. Patients with bone marrow metastatic disease will not be eligible.

               4. Adequate renal function defined as:

             i. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m² or ii. Serum
             creatinine based on age/gender as follows: Age Maximum Serum Creatinine (mg/dL) Male
             Female 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16
             years 1.5 1.4

             ≥ 16 years 1.7 1.4 The threshold creatinine values in this table were derived from
             the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985)
             utilizing child length and stature data published by the CDC.

             iii. Urine protein: ≤ 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative
             protein is < 1000 mg in a 24 hour urine sample.

             e. Adequate liver function defined as: i. Bilirubin (sum of conjugated +
             unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age ii. SGPT (ALT) ≤ 110 U/L.
             For the purpose of this study, the ULN for SGPT is 45 U/L iii. Serum albumin ≥ 2.8
             g/dL f. Adequate coagulation status defined as: PT and INR ≤ 1.5x ULN g. Adequate
             pancreatic function defined as: Serum amylase and lipase ≤ 1.5 x ULN h. Adequate
             blood pressure control defined as: A blood pressure (BP) ≤ the 95th percentile for
             age, height and gender and not receiving medication for treatment of hypertension.
             Please note that 3 serial blood pressures should be obtained and averaged to
             determine baseline BP.

             i. Central nervous system function defined as: Patients with seizure disorder may be
             enrolled if receiving non-enzyme inducing anticonvulsants and well controlled.

             j. Adequate cardiac function defined as: i. No history of congenital QTc syndrome,
             NYHA Class III or IV congestive heart failure (CHF) ii. No clinical significant
             cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to
             enrollment iii. QTc ≤ 480 msec. Note: Patients with Grade 1 prolonged QTc (450-480
             msec) at the time of study enrollment should have correctable causes of prolonged QTc
             addressed if possible (i.e., electrolytes, medications).

          9. Informed consent: All patients and/or their parents or legally authorized
             representatives must sign a written informed consent. Assent, when appropriate, will
             be obtained according to institutional guidelines.

         10. Archival tumor tissue slides must be sent or available.

        Exclusion Criteria:

          1. Pregnancy or Breastfeeding: Pregnant or breastfeeding women will not be entered on
             this study due to risks of fetal and teratogentic adverse events as seen in
             animal/human studies. Pregnancy tests must be obtained in girls who are
             post-menarchal. Males or females of reproductive potential may not participate unless
             they have agreed to use two methods of birth control- a medically accepted barrier
             method of contraceptive method (e.g., male or female condom) and a second effective
             method of birth control during protocol therapy and for at least 4 months after the
             last dose of cabozantinib. Abstinence is an acceptable method of birth control.

          2. Concomitant Medications:

               1. Corticosteroids: Patients receiving corticosteroids who have not been on a
                  stable or decreasing dose of corticosteroid for at least 7 days prior to
                  enrollment are not eligible.

               2. Investigational drugs: Patients who are currently receiving another
                  investigational drug are not eligible.

               3. Anti-cancer agents: Patients who are currently receiving other anti-cancer
                  agents are not eligible.

               4. CYP3A4 active agents: Patients must not be receiving any of the following potent
                  CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole,
                  azithromycin, itraconazole, grapefruit juice or St. John's wort. A list of other
                  known CYP3A4 inducers and inhibitors that should be discontinued prior to
                  initiation of protocol therapy and should be avoided during study therapy if
                  reasonable alternatives exist is included in Appendix V.

               5. Patients who are receiving systemic treatment anticoagulation are not eligible.
                  Patients receiving prophylactic systemic anticoagulation will be allowed as long
                  as eligibility PT/INR requirements are met.

               6. Enzyme-inducing anticonvulsants: Patients must not have received enzyme-inducing
                  anticonvulsants within 14 days prior to enrollment

               7. QTc Agents: Patients who are receiving drugs that prolong QTc are not eligible.

          3. Patients with active bleeding are not eligible. Specifically, no clinically
             significant GI bleeding, GI perforation, intra-abdominal abscess or fistula for 6
             months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for
             3 months prior to enrollment.

          4. Patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or
             MRI are not eligible (patients with evidence of resolving hemorrhage will be
             eligible).

          5. Surgery: Patients who have had or are planning to have the following invasive
             procedures are not eligible:

          6. Major surgical procedure, laparoscopic procedure, open biopsy or significant
             traumatic injury within 28 days prior to enrollment.

          7. Central line placement or subcutaneous port placement is not considered major surgery
             but must be placed at least 3 days prior to enrollment for external lines (e.g.,
             Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port.

          8. Patients must be able to swallow intact tablets. Patients who cannot swallow intact
             tablets are not eligible.

          9. Core biopsy within 7 days prior to enrollment.

         10. Fine needle aspirate within 7 days prior to enrollment.

         11. Surgical or other wounds must be adequately healed prior to enrollment.

         12. Patients on antihypertensive therapy for control of blood pressure at the time of
             enrollment are not eligible.

         13. Patients with any medical or surgical conditions that would interfere with
             gastrointestinal absorption of this oral agent are not eligible.

         14. Infection: Patients who have an uncontrolled infection are not eligible.

         15. Patients who have received a prior solid organ transplantation are not eligible.

         16. Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study are not eligible.

         17. Subjects who have received cabozanitnib or have an allergy to cabozantinib are
             excluded. Subjects who have previously received tyrosine kinase inhibitors are
             allowed.

         18. Subjects who have not received radiation therapy as part of their prior treatment are
             excluded.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease response
Time Frame:6 months
Safety Issue:
Description:Response criteria are assessed based on the product of the longest diameter and its longest perpendicular diameter. Complete response (CR): Disappearance of all target lesions Partial response (PR): ≥50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements Stable disease (SD): Neither sufficient decrease in the sum of the products of the two perpendicular diameters of all target lesions to qualify for PR, nor sufficient increase in a single target lesion to qualify for PD. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Indiana University

Trial Keywords

  • High Grade Glioma
  • Cabozantinib

Last Updated

August 26, 2016