Clinical Trial: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase 2 Trial of XL184 (Cabozantinib) an Oral Small-Molecule Inhibitor of Multiple Kinases, in Children and Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors

Brief Summary: This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have come back, do not respond to therapy, or are newly diagnosed. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth and tumor blood vessel growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the objective response rate (complete response + partial response) of cabozantinib-s-malate (XL184) in children and young adults.

SECONDARY OBJECTIVES:

I. To further define XL184 related toxicities in pediatric, adolescent and young adult patients.

II. To further define XL184 pharmacokinetics in the pediatric and adolescent patients.

TERTIARY OBJECTIVES:

I. To estimate 1-year time to progression, progression free survival (PFS) and overall survival for each stratum, and if feasible to compare to historical controls.

II. To assess the effect of XL184 on patients' immune cell subsets. III. To obtain tumor tissue (snap frozen, formalin-fixed and paraffin-embedded [FFPE] blocks, or unstained slides) from diagnosis, recurrence, or both, for possible future studies.

OUTLINE:

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, every 6 months for 1 year and then annually for up to 5 years.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 1 year ]

Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. Will be assessed using the exact conditional test of proportions.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]
    Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
  • Pharmacokinetics (PK) parameters of cabozantinib s-malate [ Time Frame: Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1, and prior to dose and 2-4 hours after dose on day 22 of course 1 ]
    The PK parameters such as peak concentration, time to peak concentration, area under the curve (AUC), apparent clearance, half-life, and steady state concentration will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. Will also be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 15, 2016
Date Started: July 19, 2017
Date Completion: November 21, 2018
Last Updated: April 23, 2017
Last Verified: April 2017