Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors

NCT01709435 | Completed Phase 1 Results

• 7 other identifiers: NCI-2012-01890P121149COG-ADVL1211NCI-2013-01571CDR0000741914ADVL1211UM1CA097452
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 23

Brief Summary

This phase I trial studies the side effects and best dose of cabozantinib S-malate in treating younger patients with solid tumors that have come back or no longer respond to treatment. Cabozantinib S-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Primary Central Nervous System Neoplasm; Recurrent Thyroid Gland Carcinoma; Refractory Malignant Solid Neoplasm; Refractory Primary Central Nervous System Neoplasm; Thyroid Gland Medullary Carcinoma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose of Cabozantinib S-malate

  Maximum dose at which fewer than one-third of toxicity-evaluable patients experience a dose limiting toxicity during cycle 1 of therapy.

  Up to 28 days

• Number of Evaluable Patients With Dose Limiting Toxicities of Cabozantinib

  Number of toxicity-evaluable patients who experience a dose limiting toxicity during cycle 1 of therapy stratified by dose level and study part.

  Up to 28 days

• Clearance of Cabozantinib S-malate

  Median (min, max) clearance of cabozantinib stratified by dose level and study part post-dose in cycle 1, day 1.

  Up to 24 hours

Secondary Outcomes (4)

• Disease Response of Cabozantinib S-malate

  Up to 5 years

• Overall Survival (OS) of Cabozantinib S-malate

  Up to 5 years

• Change From Baseline in VEGF-R2 Concentration

  Up to 28 days

• Biomarker Response (CEA and Calcitonin) in Patients With Medullary Thyroid Cancer Treated With XL184

  Up to 28 days

Study Arms (1)

Treatment (cabozantinib S-malate)

EXPERIMENTAL

Patients receive cabozantinib S-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Treatment (cabozantinib S-malate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib S-malate)

Pharmacological Study OTHER

Correlative studies

Treatment (cabozantinib S-malate)

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a body surface area \>= 0.44 m\^2 when enrolling on dose level -1; patients must have a body surface area \>= 0.35 m\^2 when enrolling on dose level 1, 2, or 3
• PART A: Patients with relapsed or refractory solid tumors (excluding medullary thyroid cancer) including CNS tumors and malignant melanoma are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Part B: Patients with medullary thyroid cancer (MTC), with or without bone marrow involvement, will be eligible for Part B; these patients will be enrolled at dose level 2, the recommended phase 2 dose determined in the dose escalation part of the study
• Patients must have either measurable or evaluable disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
• Note: neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; 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 anti-cancer chemotherapy:
• Myelosuppressive chemotherapy: at least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
• Radiation therapy (XRT): at least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
• Stem cell infusion without TBI: no evidence of active graft versus (vs.) host disease and at least 56 days must have elapsed after transplant or stem cell infusion

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study; 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 contraceptive 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
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
• 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 graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients must not be receiving any of the following potent cytochrome P450 family 3, subfamily A, polypeptide 4 cytochrome (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort
• Patients who are receiving systemic treatment anticoagulation are not eligible; patients receiving prophylactic systemic anticoagulation will be allowed as long as eligibility PT/INR requirements are met
• 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 must be able to swallow intact tablets; patients who cannot swallow intact tablets 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 computed tomography (CT) or magnetic resonance imaging (MRI) are not eligible (patients with evidence of resolving hemorrhage will be eligible)
• Patients who have had or are planning to have the following invasive procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury 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) and at least 7 days prior to enrollment for subcutaneous port

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (23)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Oncology Group

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Melanoma; Central Nervous System Neoplasms; Thyroid Neoplasms; Carcinoma, Medullary

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Neoplasms; Nervous System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Carcinoma, Neuroendocrine; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Meredith K Chuk

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 18, 2012
• Study Start: November 14, 2012
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2019
• Last Updated: December 22, 2023
• Results First Posted: December 21, 2023

Record last verified: 2023-12

Locations

US (22); CA (1)