Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
Condition: Adrenal Cortex Carcinoma; Alveolar Soft Part Sarcoma; Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Tissue; Clear Cell Sarcoma of Soft Tissue; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; Osteosarcoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Clear Cell Sarcoma of Soft Tissue; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Kidney Wilms Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Recurrent Primary Malignant Central Nervous System Neoplasm; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Medullary Carcinoma; Refractory Clear Cell Sarcoma of Soft Tissue; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Hepatocellular Carcinoma; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Primary Malignant Central Nervous System Neoplasm; Refractory Renal Cell Carcinoma; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Medullary Carcinoma; Renal Cell Carcinoma; Rhabdomyosarcoma; Solid Neoplasm; Thyroid Gland Medullary Carcinoma; Wilms Tumor; Refractory Alveolar Soft Part Sarcoma; Refractory Adrenal Cortex Carcinoma; Refractory Wilms Tumor; Soft Tissue Sarcoma
MeSH terms: Carcinoma; Neoplasms; Carcinoma, Hepatocellular; Sarcoma; Carcinoma, Renal Cell; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Wilms Tumor; Nervous System Neoplasms; Hepatoblastoma; Central Nervous System Neoplasms; Carcinoma, Medullary; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Sarcoma, Alveolar Soft Part; Sarcoma, Clear Cell; Adrenocortical Carcinoma; Thyroid Diseases; Recurrence
Intervention: Cabozantinib; Cabozantinib S-malate; Pharmacological Study
Intervention description: Given PO; Given PO
Note: Capsule formulation (Cometriq) not used in this trial.; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 2 Years
Maximum age: 30 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Upper age limit of =< 18 years of age for medullary thyroid carcinoma (MTC), renal
             cell carcinoma (RCC) and hepatocellular carcinoma (HCC) =< 30 years for all other
             diagnoses

          -  Patients must have a body surface area >= 0.35 m^2

          -  Patients must have recurrent or refractory disease, or newly diagnosed disease with no
             known curative therapy or therapy proven to prolong survival with an acceptable
             quality of life; patients must have had histologic verification of one of the
             malignancies listed below at original diagnosis or at relapse:

               -  Ewing sarcoma

               -  Rhabdomyosarcoma (RMS)

               -  Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia
                  transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear
                  cell sarcoma [CCS])

               -  Osteosarcoma

               -  Wilms tumor

               -  Rare tumors

                    -  Medullary thyroid carcinoma (MTC)

                    -  Renal cell carcinoma (RCC)

                    -  Hepatocellular carcinoma (HCC)

                    -  Hepatoblastoma

                    -  Adrenal coertex carcinoma

                    -  Pediatric solid tumors (including central nervous system [CNS] tumors) with
                       known molecular alterations in the targets of XL184 (i.e., MET
                       amplification, overexpression, activating mutation, MET translocation, MET
                       exon skipping mutations, activating RET mutations, RET rearrangement,
                       overexpression or activation of AXL); documentation of the alteration from a
                       Clinical Laboratory Improvement Act (CLIA) certified laboratory will be
                       required

                         -  Note: Documentation of any known tumor molecular alterations and RET
                            mutation status for patients with MTC (germline) must be uploaded via
                            the RAVE system

          -  Patients must have radiographically measurable disease; measurable disease is defined
             as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed
             tomography (CT) scan that can be accurately measured with the longest diameter a
             minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5
             mm)

               -  Note: The following do NOT qualify as measurable disease:

                    -  Malignant fluid collections (e.g., ascites, pleural effusions)

                    -  Bone marrow infiltration

                    -  Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
                       positron emission tomography [PET] scans)

                    -  Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

                    -  Previously radiated lesions that have not demonstrated clear progression
                       post radiation

                    -  Leptomeningeal lesions that do not meet the measurement parameters noted
                       above

          -  Patients must have a Lansky or Karnofsky performance status score of >= 50,
             corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use
             Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age;
             patients who are unable to walk because of paralysis, but who are up in a wheelchair,
             will be considered ambulatory for the purpose of assessing the performance score

          -  Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study

          -  Patients with solid tumors must not have received myelosuppressive chemotherapy within
             3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)

          -  At least 7 days must have elapsed since the completion of therapy with a growth
             factor. At least 14 days must have elapsed after receiving pegfilgrastim

          -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced
             platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of
             agent

          -  Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and
             toxicity related to prior antibody therapy must be recovered to grade =< 1

          -  >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small
             port); >= 6 weeks must have elapsed since treatment with therapeutic doses of
             M-Iodobenzylguanidine (MIBG); >= 3 months must have elapsed if prior craniospinal XRT
             was received, if >= 50% of the pelvis was irradiated, or if total-body irradiation
             (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow
             irradiation was given

               -  Subjects should not have any clinically relevant ongoing complications from prior
                  radiation therapy (i.e., radiation esophagitis or other inflammation of the
                  viscera)

          -  No evidence of active graft versus (vs.) host disease and >= 2 months must have
             elapsed since transplant

          -  Not previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib);
             there are no limits on number of prior therapeutic regimens; patients who have been
             treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligible

          -  Peripheral absolute neutrophil count (ANC) >= 1000/uL for patients with solid tumors
             without bone marrow involvement

          -  Platelet count >= 100,000/uL (transfusion independent, defined as not receiving
             platelet transfusions within a 7 day period prior to enrollment) for patients with
             solid tumors without bone marrow involvement

          -  Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) for patients
             with solid tumors without bone marrow involvement

          -  Peripheral absolute neutrophil count (ANC) >= 750/uL for patients with solid tumors
             and known bone marrow metastatic disease

          -  Platelet count >= 50,000/uL for patients with solid tumors and known bone marrow
             metastatic disease

          -  Hemoglobin >= 8.0 g/dL for patients with solid tumors and known bone marrow metastatic
             disease

          -  Transfusions are permitted to meet both the platelet and hemoglobin criteria for
             patients with known bone marrow metastatic disease; patients must not be known to be
             refractory to red blood cell or platelet transfusions

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
             mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

               -  2 to < 6 years of age

                    -  Male and female: 0.8 (maximum serum creatinine [mg/dL])

               -  6 to < 10 years of age

                    -  Male and female: 1 (maximum serum creatinine [mg/dL])

               -  10 to < 13 years of age

                    -  Male and female: 1.2 (maximum serum creatinine [mg/dL])

               -  13 to < 16 years of age

                    -  Male 1.5 (maximum serum creatinine [mg/dL])

                    -  Female: 1.4 (maximum serum creatinine [mg/dL])

               -  >= 16 years of age

                    -  Male: 1.7 (maximum serum creatinine [mg/dL])

                    -  Female: 1.4 (maximum serum creatinine [mg/dL])

          -  Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative
             protein is < 1000 mg in a 24 hour (h) urine sample

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
             U/L (3 x ULN) (for the purpose of this study, the ULN for SGPT is 45 U/L)

          -  Serum albumin >= 2.8 g/dL

          -  No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart
             Association (NYHA) class III or IV congestive heart failure (CHF)

          -  No clinically significant cardiac arrhythmias, stroke or myocardial infarction within
             6 months prior to enrollment

          -  QTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time
             of study enrollment should have correctable causes of prolonged QTc addressed if
             possible (i.e., electrolytes, medications)

          -  Patients with a known seizure disorder who are receiving non-enzyme inducing
             anticonvulsants and have well-controlled seizures may be enrolled

          -  CNS toxicity =< grade 2 with the exception of decreased tendon reflex (DTR); any grade
             of DTR is eligible

          -  A blood pressure (BP) =< the 95th percentile for age, height, and gender for pediatric
             patients < 18 years old and =< 140/90 mmHg for patients >= 18 years old; patients
             should not be receiving medication for treatment of hypertension (except patients with
             Wilms tumor and RCC who may be eligible if on stable doses of no more than one
             anti-hypertensive medication with a baseline BP =< ULN for pediatric patients and =<
             140/90 for adult patients); please note that 3 serial blood pressures should be
             obtained and averaged to determine baseline BP

          -  International normalized ratio (INR) =< 1.5

          -  Serum amylase =< 1.5 x ULN

          -  Serum lipase =< 1.5 x ULN

        Exclusion Criteria:

          -  Pregnant or breast-feeding women will not be entered on this study due to risks of
             fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests
             must be obtained in girls who are post-menarchal; males or females of reproductive
             potential may not participate unless they have agreed to use two methods of birth
             control- a medically accepted barrier method of contraceptive method (e.g., male or
             female condom) and a second effective method of birth control-during protocol therapy
             and for at least 4 months after the last dose of XL184; abstinence is an acceptable
             method of birth control

          -  Growth factors that support platelet or white cell number or function must not have
             been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)

          -  Patients requiring corticosteroids who have not been on a stable or decreasing dose of
             corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify
             immune adverse events related to prior therapy, >= 14 days must have elapsed since
             last dose of corticosteroid

          -  Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib,
             crizotinib)

          -  Patients who are currently receiving another investigational drug are not eligible

          -  Patients who are currently receiving other anti-cancer agents are not eligible

          -  Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either
             graft-versus-host disease post bone marrow transplant or organ rejection
             post-transplant are not eligible for this trial

          -  Patients must not be receiving any of the following potent CYP3A4 inducers or
             inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole,
             grapefruit juice or St. John's wort

          -  Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin,
             and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited

               -  Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and
                  low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation
                  with therapeutic doses of LMWH is allowed in subjects without radiographic
                  evidence of brain metastasis, who are on a stable dose of LMWH for at least 6
                  weeks before first dose of study treatment, and who have had no complications
                  from a thromboembolic event or the anticoagulation regimen

          -  Patients must not have received enzyme-inducing anticonvulsants within 14 days prior
             to enrollment

          -  Patients who are receiving drugs that prolong QTc are not eligible

          -  Patients who are unable to swallow intact tablets are not eligible

          -  Patients who have an uncontrolled infection are not eligible

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study are not eligible

          -  Patients with active bleeding are not eligible; specifically, no clinically
             significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or
             fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary
             hemorrhage for 3 months prior to enrollment; patients with evidence of an acute
             intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with
             evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an
             MRI with ECHO gradient sequences would be required to exclude presence of petechial
             hemorrhages

          -  Patients who have had or are planning to have the following invasive procedures are
             not eligible:

               -  Major surgical procedure, laparoscopic procedure, or open biopsy within 28 days
                  prior to enrollment

               -  Central line placement or subcutaneous port placement is not considered major
                  surgery but must be placed at least 3 days prior to enrollment for external lines
                  (e.g., Hickman or Broviac catheter, peripherally inserted central catheter
                  [PICC]) and at least 7 days prior to enrollment for a subcutaneous port

               -  Core biopsy within 7 days prior to enrollment

               -  Fine needle aspirate within 7 days prior to enrollment

               -  Surgical or other wounds must be adequately healed prior to enrollment

               -  NOTE: For purposes of this study, bone marrow aspirate and biopsy are not
                  considered surgical procedures and therefore are permitted within 14 days prior
                  to start of protocol therapy

          -  Patients who have had significant traumatic injury within 28 days prior to enrollment
             are not eligible

          -  Patients with any medical or surgical conditions that would interfere with
             gastrointestinal absorption of the study drug are not eligible