Clinical Trial: Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of XL184 (Cabozantinib) in Children and Adolescents With Recurrent or Refractory Solid Tumors, Including CNS Tumors

Brief Summary: This phase I trial studies the side effects and best dose of cabozantinib S-malate in treating younger patients with solid tumors that have come back or no longer respond to treatment. Cabozantinib S-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of XL184 (cabozantinib) (cabozantinib S-malate) administered orally to children with refractory solid tumors including central nervous system (CNS) tumors.

II. To define and describe the toxicities of XL184 (cabozantinib) administered on this schedule.

III. To characterize the pharmacokinetics of XL184 (cabozantinib) in children with refractory solid tumors.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of XL184 (cabozantinib) within the confines of a phase 1 study.

II. To assess the biologic activity of XL184 (cabozantinib). III. To assess the biomarker response (carcinoembryonic antigen [CEA] and calcitonin) in patients with medullary thyroid cancer treated with XL184.

IV. To evaluate overall survival from study entry through a five-year follow-up period.

OUTLINE: This is a dose-escalation study. (Complete as of 4/16/2014)

Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 6 months, and then annually for up to 60 months.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: MTD and/or recommended phase 2 dose of cabozantinib S-malate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ]

In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.


Original Primary Outcome: MTD and/or recommended phase 2 dose of cabozantinib [ Time Frame: 28 days ]

In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.


Current Secondary Outcome:

  • Disease response assessed according to Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 5 years ]
    Will be reported descriptively.
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
    OS will also be assessed and summarized using the Kaplan-Meier method.
  • Pharmacokinetic (PK) parameters of cabozantinib S-malate including systemic exposure and drug clearance [ Time Frame: Course 1, day 1 (pre-dose and 4 hours post dose), course 1 day 21 (+/- 2 days) (pre-dose, 2, 4, 8 and 24 hours post dose), course 3 day 1 (pre-dose) ]
    Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Original Secondary Outcome:

  • Pharmacokinetic (PK) parameters of cabozantinib including systemic exposure and drug clearance [ Time Frame: Course 1, day 1 (pre-dose and 4 hours post dose), course 1 day 21 (+/- 2 days) (pre-dose, 2, 4, 8 and 24 hours post dose), course 3 day 1 (pre-dose) ]
    Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
  • Disease response assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 2 years ]
    Will be reported descriptively.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 16, 2012
Date Started: November 2012
Date Completion:
Last Updated: May 18, 2017
Last Verified: May 2017