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
3 other identifiers
interventional
109
1 country
142
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2017
Longer than P75 for phase_2
142 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 15, 2016
CompletedFirst Posted
Study publicly available on registry
August 16, 2016
CompletedStudy Start
First participant enrolled
May 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2021
CompletedResults Posted
Study results publicly available
November 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 27, 2026
ExpectedJune 11, 2026
December 1, 2025
4.1 years
August 15, 2016
August 11, 2022
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
Up to the first 6 cycles of therapy.
Secondary Outcomes (9)
Percentage of Participants With Adverse Events
Up to 5 years (duration of protocol therapy plus 30 days after last dose of therapy)
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Cmax
Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Tmax
Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: AUC
Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Accumulation
Cycle 1, Day 1 (20-28 hours after dose) and Cycle 1, Day 22
- +4 more secondary outcomes
Other Outcomes (1)
Change in Immune Biomarkers
Baseline, day 1 (prior to dose) of cycles 2 and 3
Study Arms (1)
Treatment (cabozantinib s-malate)
EXPERIMENTALPatients 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.
Interventions
Given PO Note: Capsule formulation (Cometriq) not used in this trial.
Eligibility Criteria
You may qualify if:
- 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
- +52 more criteria
You may not qualify if:
- 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
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (142)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente-Anaheim
Anaheim, California, 92806, United States
Kaiser Permanente-Bellflower
Bellflower, California, 90706, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Kaiser Permanente-Fontana
Fontana, California, 92335, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027, United States
Valley Children's Hospital
Madera, California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Kaiser Permanente-San Diego Mission
San Diego, California, 92108, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Kaiser Permanente-Capitol Hill Medical Center
Washington D.C., District of Columbia, 20002, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Straub Clinic and Hospital
Honolulu, Hawaii, 96813, United States
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
The Carle Foundation Hospital
Urbana, Illinois, 61801, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
Iowa Lutheran Hospital
Des Moines, Iowa, 50316, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236, United States
Huron Medical Center PC
Port Huron, Michigan, 48060, United States
Corewell Health Children's
Royal Oak, Michigan, 48073, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Henderson, Nevada, 89052, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144, United States
Hope Cancer Care of Nevada-Pahrump
Pahrump, Nevada, 89048, United States
Radiation Oncology Associates
Reno, Nevada, 89509, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534, United States
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Flower Hospital
Sylvania, Ohio, 43560, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Saint Francis Hospital
Greenville, South Carolina, 29601, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Saint Francis Cancer Center
Greenville, South Carolina, 29607, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Texas Tech University Health Sciences Center-El Paso
El Paso, Texas, 79905, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PMID: 31401903DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Srivandana Akshintala
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 15, 2016
First Posted
August 16, 2016
Study Start
May 18, 2017
Primary Completion
June 30, 2021
Study Completion (Estimated)
June 27, 2026
Last Updated
June 11, 2026
Results First Posted
November 28, 2022
Record last verified: 2025-12