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.
PRIMARY OBJECTIVES: I. To determine the objective response rate (complete response + partial response) of cabozantinib-s-malate (XL184) in children and young adults with Ewing sarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, and Wilms tumor. 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. 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. 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. EXPLORATORY OBJECTIVES: 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. OUTLINE: Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
109
Given PO
Given PO Note: Capsule formulation (Cometriq) not used in this trial.
Correlative studies
Children's Hospital of Alabama
Birmingham, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Kaiser Permanente-Bellflower
Bellflower, California, United States
Objective Response (Non-Osteosarcoma Strata)
Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Response rates will be calculated as the percent of evaluable patients who are responders (Overall Best Response of Partial Response or Complete Response), and confidence intervals will be constructed accounting for the two-stage design.
Time frame: Up to the first 6 cycles of therapy
Objective Response (Osteosarcoma Stratum)
Will be assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 and Disease Control (see section 9.3.2 of the ADVL1622 Protocol). Response + Disease Control rate will be calculated as the percent of evaluable patients who are responders or who met the definition of disease control, and confidence intervals will be constructed accounting for the two-stage design.
Time frame: Up to the first 6 cycles of therapy.
Percentage of Participants With Adverse Events
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy
Time frame: Up to 5 years (duration of protocol therapy plus 30 days after last dose of therapy)
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Cmax
Day 1 PK peak concentration will be summarized by the mean and the standard deviation.
Time frame: Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Tmax
Day 1 PK time to peak concentration will be summarized by the mean and the standard deviation.
Time frame: Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: AUC
Day 1 PK area under the curve will be summarized by the mean and the standard deviation.
Time frame: Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Accumulation
PK accumulation will be summarized by the mean and the standard deviation.
Time frame: Cycle 1, Day 1 (20-28 hours after dose) and Cycle 1, Day 22
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Half-life
PK half-life will be summarized by the mean and the standard deviation.
Time frame: Cycle 1, Day 1 (20-28 hours after dose) and Cycle 1, Day 22
Time to Progression (TTP)
Percent of patients not yet progressed at 1 year as estimated by the Kaplan-Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Clinical progression was also counted as an event for this analysis.
Time frame: Up to 1 year
Progression Free Survival (PFS)
The 1-year Progression Free Survival will be estimated using Kaplan-Meier methodology. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Up to 1 year
Overall Survival (OS)
The 1-year Overall Survival will be estimated using Kaplan-Meier methodology.
Time frame: Up to 1 year
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Kaiser Permanente Downey Medical Center
Downey, California, United States
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Fontana, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
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Los Angeles, California, United States
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