A Phase I Study of Pazopanib as a Single Agent for Children With Refractory Solid Tumors

NCT01130623 | Withdrawn Phase 1

• 2 other identifiers: 10012010-C-0120
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Pazopanib, a drug that inhibits the growth of new blood vessels in tumors, was recently approved by the Food and Drug Administration to treat advanced kidney cancer in adults. Pazopanib has been used in only a small number of adults, and more research is needed on whether it is safe and effective to use in children. Researchers are interested in determining safe and effective treatment doses of pazopanib in children, and in other studies will examine which form of pazopanib treatment (tablet or liquid) is most effective and well tolerated. Objectives:

• To determine a safe and effective dose of pazopanib to treat solid tumors in children.
• To study the effects of pazopanib on blood cells, blood flow, and human development. Eligibility: \- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid tumors that have not responded to treatment. Design:
• Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.
• Participants will receive pazopanib tablets for 28-day cycles of treatment. Pazopanib should be taken on an empty stomach, at least 1hour before or 2 hours after a meal. Participants may receive pazopanib for up to 24 cycles unless the tumor does not respond or participants develop serious side effects.
• Blood samples will be taken on days 1, 15, 22, and 27 of the first cycle of pazopanib, with additional samples taken every 8 weeks during subsequent cycles.
• An optional part of the study will collect additional blood samples at regular intervals for 24 hours after the first dose of pazopanib and at regular intervals after another dose during the second or third week of the first treatment cycle.

Conditions

Sarcoma; Neuroblastoma; Wilms Tumor; Osteosarcoma; Brain Tumor

Keywords

VEGF Inhibitor; Maximum Tolerated Dose; Dose Escalation; Pharmacokinetics; Antitumor Activity; Pediatric Cancer; Solid Tumor; Sarcoma; Neuroblastoma; Wilms Tumor; Osteosarcoma; Brain Tumor

Outcome Measures

Primary Outcomes (3)

• To estimate MTD and Phase II dose of oral pazopanib.

• To define the toxicities of oral pazopanib tablet or suspension.

• To characterize PKs.

Secondary Outcomes (1)

• To define antitumor and biologic activity and explore changes in tumor vascular permeability. To assess VEGF haplotype/phenotype relationships and explore concentration-effect with biomarkers and clinical outcomes.

Interventions

Pazopanib (GW786034) DRUG

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

* Eligibility: * Part 1 (Phase I Dose Escalation) and 2a (Suspension Formulation Component): --Patients greater than 12 months and less than or equal to 21 years of age with measureable or evaluable relapsed or refractory solid tumors including CNS tumors with histologic verification except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevation of tumor markers. * Part 2b (Expanded Imaging Cohort): --Patients greater than 2 years and less than or equal to 25 years of age with histologically verified relapsed or refractory soft tissue sarcoma, desmoplastic small round cell tumor or extraosseus Ewing sarcoma with measurable disease (greater than or equal to 2 cm) in the head, neck, extremity or fixed within the thorax, abdomen or pelvis. * Performance score: Karnofsky greater than or equal to 50% for patients 16 years of age; Lansky greater than or equal to 50 for patients less than or equal to 16 years of age. * Must have fully recovered from acute toxic effects from all prior therapy which have been completed within the specified prior time frame. Have adequate organ function as determined by laboratory evaluation.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. doi: 10.1016/s0092-8674(00)81683-9. No abstract available.

  PMID: 10647931 BACKGROUND

• Bigler SA, Deering RE, Brawer MK. Comparison of microscopic vascularity in benign and malignant prostate tissue. Hum Pathol. 1993 Feb;24(2):220-6. doi: 10.1016/0046-8177(93)90304-y.

  PMID: 8432518 BACKGROUND

• Bochner BH, Cote RJ, Weidner N, Groshen S, Chen SC, Skinner DG, Nichols PW. Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst. 1995 Nov 1;87(21):1603-12. doi: 10.1093/jnci/87.21.1603.

  PMID: 7563203 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Neuroblastoma; Wilms Tumor; Osteosarcoma; Brain Neoplasms; Neoplasms

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: May 10, 2010
• Primary Completion: November 18, 2011
• Study Completion: November 18, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-11-18

Locations

US (1)