Adrenal Cortical CarcinomaPhase 2NCT02867592
Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
A Phase 2 study testing Cabozantinib, Cabozantinib S-malate and Pharmacological Study in people with Adrenal Cortical Carcinoma and Alveolar Soft Part Sarcoma, run by National Cancer Institute (NCI) at 142 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Adrenal Cortical Carcinoma, Alveolar Soft Part Sarcoma, Central Nervous System Neoplasm
- What is being tested?
- Cabozantinib, Cabozantinib S-malate and Pharmacological Study
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 142 sitesUnited States
- Study dates
- 18 May 2017to 28 Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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])
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
142 sites in 1 country.
142 sites in 1 country
United States142 sites
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Providence Alaska Medical Center
Anchorage, Alaska, 99508
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
Kaiser Permanente-Bellflower
Bellflower, California, 90706
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Nationwide Children's Hospital
Columbus, Ohio, 43205
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Carle at The Riverfront
Danville, Illinois, 61832
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Iowa Lutheran Hospital
Des Moines, Iowa, 50316
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Duke University Medical Center
Durham, North Carolina, 27710
Carle Physician Group-Effingham
Effingham, Illinois, 62401
El Paso Children's Hospital
El Paso, Texas, 79905
Texas Tech University Health Sciences Center-El Paso
El Paso, Texas, 79905
Kaiser Permanente-Fontana
Fontana, California, 92335
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534
East Carolina University
Greenville, North Carolina, 27834
Saint Francis Hospital
Greenville, South Carolina, 29601
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Henderson, Nevada, 89052
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Loma Linda University Medical Center
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Hope Cancer Care of Nevada-Pahrump
Pahrump, Nevada, 89048
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Huron Medical Center PC
Port Huron, Michigan, 48060
Oregon Health and Science University
Portland, Oregon, 97239
Radiation Oncology Associates
Reno, Nevada, 89509
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Corewell Health Children's
Royal Oak, Michigan, 48073
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Kaiser Permanente-Rio San Diego
San Diego, California, 92108
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
ProMedica Flower Hospital
Sylvania, Ohio, 43560
State University of New York Upstate Medical University
Syracuse, New York, 13210
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Carle Cancer Center
Urbana, Illinois, 61801
The Carle Foundation Hospital
Urbana, Illinois, 61801
Kaiser Permanente-Capitol Hill Medical Center
Washington D.C., District of Columbia, 20002
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Adrenal Cortical Carcinoma, Alveolar Soft Part Sarcoma, Central Nervous System Neoplasm, Childhood Clear Cell Sarcoma of Soft Tissue, Clear Cell Sarcoma of Soft Tissue, Ewing Sarcoma
- Being tested
- Cabozantinib, Cabozantinib S-malate, Pharmacological Study
- Medical subject headings
- Adrenocortical Carcinoma, Sarcoma, Alveolar Soft Part, Central Nervous System Neoplasms, Sarcoma, Clear Cell, Sarcoma, Ewing, Hepatoblastoma, Carcinoma, Hepatocellular, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Given PO
Cabozantinib S-malateDrug
Also called BMS-907351, Cabometyx, Cometriq, XL 184
Given PO
Note: Capsule formulation (Cometriq) not used in this trial.
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cabozantinib s-malate) | Experimental | 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. Receives: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to the first 6 cycles of therapy.
Secondary outcomes (9)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Up to 1 year
Overall Survival (OS)
The 1-year Overall Survival will be estimated using Kaplan-Meier methodology.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study start18 May 2017
- Primary completion30 Jun 2021
- Study completion28 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal Cortical CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Srivandana Akshintala, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02867592
- Sponsor's protocol ID
- NCI-2016-01258
- Other IDs
- NCI-2016-01258, ADVL1622, ADVL1622, ADVL1622, U10CA180886
- Status last verified
- Jun 2026
- First submitted
- 15 Aug 2016
- Last updated
- 28 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 31401903