Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Thyroid Diseases

Carcinoma, Renal Cell

Sarcoma

Osteosarcoma

Wilms Tumor

Central Nervous System Neoplasms

Sarcoma, Ewing

Nervous System Neoplasms

Adrenocortical Carcinoma

Carcinoma, Medullary

Rhabdomyosarcoma

Hepatoblastoma

Sarcoma, Alveolar Soft Part

Sarcoma, Clear Cell

Thyroid Neoplasms

Carcinoma, Neuroendocrine

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neoplasms, Connective and Soft Tissue

Endocrine System Diseases

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Soft Tissue Sarcoma

Wilms' Tumor

Ewing Sarcoma

Thyroid Cancer, Medullary

Alveolar Soft Part Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

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.

Cabozantinib

Given PO

Note: Capsule formulation (Cometriq) not used in this trial.

Cabozantinib S-malate

Pharmacological Study

Srivandana Akshintala

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.

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

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

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.

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.

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.

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

Day 1 PK peak concentration will be summarized by the mean and the standard deviation.

Day 1 PK time to peak concentration will be summarized by the mean and the standard deviation.

Day 1 PK area under the curve will be summarized by the mean and the standard deviation.

PK accumulation will be summarized by the mean and the standard deviation.

PK half-life will be summarized by the mean and the standard deviation.

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.

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

The 1-year Overall Survival will be estimated using Kaplan-Meier methodology.

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Patients receive cabozantinib-s-malate (XL184), 40mg/m2/day 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.

Ewing's Sarcoma

Non-Rhabdomyosarcoma Soft Tissue Sarcoma

Rare Tumors

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol in non-osteosarcoma strata which were either statistical strata (Ewing's Sarcoma, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, and Rare Tumors) or accrued enough patients to be analyzed (Wilms Tumor). Data is limited for Rare tumors due to low accrual.

Objective Response (Non-Osteosarcoma Strata)

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol in the osteosarcoma stratum.

Objective Response (Osteosarcoma Stratum)

All patients who met the evaluable for toxicity criteria outlined in section 9.5 of the ADVL1622 protocol.

Percentage of Participants With Adverse Events

All Pharmacokinetic Patients

All patients who consented to PK or were required to consent to PK and had enough samples to estimate the PK Parameter of interest.

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Cmax

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Tmax

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: AUC

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Accumulation

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Half-life

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol.

Spots Global Cancer Trial Database for refractory alveolar soft part sarcoma