Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children

NCT02885324 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IUSCC-0601
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma; Malignant Brain Tumor; High Grade Glioma

Keywords

High Grade Glioma; Cabozantinib; GBM; Children; AA

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Disease Response

  To assess the number of participants with best response of CR, PR, SD or PD. 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.

  6 months

Secondary Outcomes (2)

• Overall Survival

  6 months

• Number of Participants With Progression Free Survival

  6 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Cabozantininb 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.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Subjects will receive Cabozantinib

Also known as: XL 184, Cabometyx

Cabozantinib

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be ≥2 years and ≤21 years of age
• Diagnosis: Patients with relapsed or refractory central nervous system tumors. Patients must have had histological verification of malignancy at original diagnosis or relapse. Metastatic disease to the spine or primary tumors in the spine are eligible. Patients may be in first, second, or third relapse. Subjects with intrinsic brain stem gliomas may be eligible with or without histological confirmation. Please contact study chair prior to enrollment.
• Disease Status: Patients must have measurable disease. Linear enhancement of leptomeningeal without measurable mass is excluded.
• Therapeutic Options: Patient's current disease state must be one for which there is no accepted standard therapy, no known curative therapy or therapy proven to prolong survival with an acceptable quality of life. For patients in whom surgery is feasible, maximal surgical resection must have occurred.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix 1). 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.
• Subjects must have a reasonable life expectancy of at least 2 months.
• Prior Therapy
• a. Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy i. Cytotoxic chemotherapy (including investigational agents) or biologic agents (eg. Cytokines or antibodies): At least 3 weeks after the last dose.
• ii. Nitrosoureas/mitomycin C: At least 6 weeks from the last dose. iii. 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: No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion.
• Organ Function Requirements:
• a. Adequate bone marrow function defined as: absolute neutrophil count (ANC ≥1000/mm3) i. Platelet count ≥ 100,000/ mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) ii. Patients with bone marrow metastatic disease will not be eligible. b. Adequate renal function defined as: i. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m² or a 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.
• ii. Urine protein: ≤ 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is \< 1000 mg in a 24 hour urine sample.
• c. Adequate Liver Function Defined as:

You may not qualify if:

• Pregnancy or Breast-Feeding: Pregnant or breast-feeding 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.
• Concomitant Medications:
• 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.
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible.
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible.
• 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.
• Patients who are receiving systemic therapeutic treatment anticoagulation are not eligible. Patients receiving prophylactic systemic anticoagulation will be allowed with heparin or LMWH as long as eligibility PT/INR requirements are met. Concomitant anticoagulation with oral anticoagulations (e.g. warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg. Clopidogrel) are not allowed.
• Enzyme-inducing anticonvulsants: Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment (See Appendix III for a list of unacceptable enzyme inducing anticonvulsants).
• QTc Agents: Patients who are receiving drugs that prolong QTc are not eligible (See Appendix IV for a list of agents).
• Patients must be able to swallow intact tablets. Patients who cannot swallow intact tablets are not eligible.
• 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.
• 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).
• Major surgery within 28 days of enrollment. Complete wound healing from major or minor surgery must have occurred prior to enrollment. Minor surgery (including uncomplicated tooth extractions) within 7 days of enrollment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible;
• Concurrent uncontrolled hypertension defined as sustained blood pressure\>95% for age, height and gender (systolic or diastolic) despite optimal antihypertensive treatment within 7 days of the first dose of study treatment.
• Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of this oral agent are not eligible.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Riley Hospital for Children at IU Health

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Brain Neoplasms; Glioma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Scott Coven
• Organization: Indiana University

scoven@iu.edu

317-944-8784

Study Officials

• Scott Coven, DO

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 24, 2016
• First Posted: August 31, 2016
• Study Start: May 18, 2017
• Primary Completion: August 25, 2020
• Study Completion: August 25, 2020
• Last Updated: October 6, 2022
• Results First Posted: August 15, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)