Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
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|ClinicalTrials.gov Identifier: NCT02867592|
Recruitment Status : Recruiting
First Posted : August 16, 2016
Last Update Posted : June 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adrenal Cortex Carcinoma Adult Alveolar Soft Part Sarcoma Adult Clear Cell Sarcoma of Soft Parts Adult Hepatocellular Carcinoma Adult Rhabdomyosarcoma Adult Soft Tissue Sarcoma Childhood Alveolar Soft Part Sarcoma Childhood Central Nervous System Neoplasm Childhood Clear Cell Sarcoma of Soft Parts Childhood Hepatocellular Carcinoma Childhood Rhabdomyosarcoma Childhood Soft Tissue Sarcoma Childhood Solid Neoplasm Ewing Sarcoma Hepatoblastoma Hepatocellular Carcinoma Recurrent Adrenal Cortex Carcinoma Recurrent Adult Hepatocellular Carcinoma Recurrent Adult Soft Tissue Sarcoma Recurrent Alveolar Soft Part Sarcoma Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Hepatocellular Carcinoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma Recurrent Hepatoblastoma Recurrent Malignant Solid Neoplasm Recurrent Osteosarcoma Recurrent Renal Cell Carcinoma Recurrent Rhabdomyosarcoma Refractory Osteosarcoma Renal Cell Carcinoma Thyroid Gland Medullary Carcinoma Wilms Tumor||Drug: Cabozantinib S-malate Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 2|
I. To determine the objective response rate (complete response + partial response) of cabozantinib-s-malate (XL184) in children and young adults.
II. To estimate whether XL184 therapy either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to a historical Childrens Oncology Group (COG) experience or produces an objective response rate.
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.
III. 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.
I. To assess the effect of XL184 on patients' immune cell subsets. II. 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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||146 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 8, 2017|
|Estimated Primary Completion Date :||November 21, 2018|
|Estimated Study Completion Date :||November 21, 2018|
Experimental: Treatment (cabozantinib s-malate)
Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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.
- 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, prior to dose on day 1 of courses 2 and 3 ]The PK parameters such as peak concentration, time to peak concentration, area under the curve, 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).
- Progression free survival (PFS) [ Time Frame: Up to 1 year ]Will be assessed using the log-rank test with hazard ratios estimated from a Cox proportional hazards regression model. Will compare PFS to historical controls.
- Change in immune biomarkers [ Time Frame: Baseline up to course 3, day 1 ]The association between the host immune system and response to cabozantinib-s-malate will be assessed in an exploratory manner. each biomarker will be correlated with the clinical outcomes of objective response and progression free survival.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867592
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|Principal Investigator:||Srivandana Akshintala||Children's Oncology Group|