Sunitinib in Treating Young Patients With Refractory Solid Tumors

NCT ID: NCT00387920

Last Updated: 2014-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31

Brief Summary

This phase I trial is studying the side effects and best dose of sunitinib in treating young patients with refractory solid tumors. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and recommended phase II dose of sunitinib malate in pediatric patients with refractory solid tumors.

II. Determine the toxicity of this regimen in these patients. III. Characterize the pharmacokinetics of this regimen in these patients. IV. Evaluate the tolerability and pharmacokinetic profile of sunitinib malate capsule contents sprinkled over applesauce or yogurt using the recommended phase II dose.

SECONDARY OBJECTIVES:

I. Determine, preliminarily, the antitumor effects of this regimen in these patients.

II. Describe changes in peripheral blood monocyte counts, circulating endothelial cells, and plasma angiogenic factors during treatment with sunitinib malate.

III. Explore changes in tumor vascular permeability using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) in patients receiving sunitinib malate.

OUTLINE: This is a multicenter, dose-escalation study (part A) followed by a pediatric-friendly formulation study (part B).

PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sunitinib malate until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.

NOTE: Patients will not receive sunitinib malate on day 2 of the first course to allow for pharmacokinetic testing.

Blood is collected on days 1, 7, 14, 21, and 28 of course 1 for pharmacokinetic studies using liquid chromatography/mass spectrometry.

After completion of study treatment, patients are followed up for 30 days.

Conditions

Central Nervous System Metastases; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor therapy)

PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.

Group Type: EXPERIMENTAL

sunitinib malate

Intervention Type: DRUG

Given orally

pharmacological study

Intervention Type: OTHER

Correlative studies

dynamic contrast-enhanced magnetic resonance imaging

Intervention Type: PROCEDURE

Undergo DCE-MRI

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

sunitinib malate

Given orally

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

dynamic contrast-enhanced magnetic resonance imaging

Undergo DCE-MRI

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

SU11248; sunitinib; Sutent; pharmacological studies; DCE-MRI

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed solid tumor (not required for patients with intrinsic brain stem tumors or optic pathway gliomas)

• Recurrent or refractory disease
• Measurable or evaluable disease
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
• Patients with metastatic bone marrow disease are eligible but are not evaluable for hematologic toxicity

• Must not be refractory to red blood cell or platelet transfusions
• Primary CNS tumors or known CNS metastases allowed

• Neurological deficits must have been relatively stable for ≥ 1 week before study enrollment
• No imaging evidence of prior intracranial hemorrhage
• No evidence of new CNS hemorrhage on baseline MRI obtained within 14 days before study enrollment (ECHO gradient MRI sequences per institutional guidelines required for evaluation of CNS hemorrhage)

• The presence of small punctuate CNS hemorrhage on these scans will exclude a patient from participation
• No known bone marrow metastatic disease
• No tumors involving the pleural surface
• Karnofsky performance status (PS) 50-100% (> 10 years of age) OR Lansky PS 50-100% (≤ 10 years of age)
• Absolute neutrophil count ≥ 1,000/mm³*
• Platelet count ≥ 100,000/mm³ (transfusion independent)*
• Hemoglobin ≥ 8.0 g/dL (transfusions allowed)*
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age/gender as follows:

• No greater than 0.8 mg/dL (2 to 5 years of age)
• No greater than 1 mg/dL (6 to 9 years of age)
• No greater than 1.2 mg/dL (10 to 12 years of age)
• No greater than 1.5 mg/dL (male) OR 1.4 mg/dL (female) (13 to 15 years of age)
• No greater than 1.7 mg/dL (male) OR 1.4 mg/dL (female) (≥ 16 years of age)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
• Albumin ≥ 2 g/dL
• LVEF or shortening fraction normal
• Corrected QT interval ≤ 450 msec
• Amylase ≤ 1.5 times ULN
• Lipase ≤ 1.5 times ULN
• Body surface area ≥ 0.5 m² (≥ 0.4 m² for part B)
• Blood pressure within ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No uncontrolled infection
• Able to swallow sunitinib malate capsules (part A only)
• No pre-existing thyroid abnormality (hyper- or hypothyroidism) with unstable thyroid function
• No prior CNS hemorrhage
• No history of allergic reaction attributed to sunitinib malate or component of sunitinib malate capsules
• No allergy to both applesauce and yogurt (part B only)
• Recovered from prior therapy
• No prior sunitinib malate
• No prior anthracycline (any dose)
• No prior radiotherapy to a radiation field that included the heart(including total body or craniospinal irradiation)
• At least 3 months since prior stem cell transplantation or rescue (without total-body irradiation) and no evidence of graft-vs-host disease
• At least 2 weeks since prior local, palliative, small-port radiotherapy (at least 6 months for radiation to ≥ 50% of pelvis)
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas)
• At least 1 week since prior antineoplastic biologic agents
• At least 1 week since prior and no concurrent hematopoietic growth factors
• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

• Rifampin
• Rifabutin
• Carbamazepine
• Phenobarbital
• Phenytoin
• Hypericum perforatum (St. John's wort)
• Efavirenz
• Tipranavir
• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

• Azole antifungals (e.g., itraconazole or ketoconazole)
• Clarithromycin
• Erythromycin
• Diltiazem
• Verapamil
• HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
• Delavirdine
• No more than 1 concurrent antihypertensive agent
• No concurrent major surgery
• No concurrent antithrombotic or antiplatelet agents, including any of the following:

• Warfarin
• Heparin
• Low molecular weight heparin
• Acetylsalicylic acid (aspirin)
• Ibuprofen
• Other nonsteroidal anti-inflammatory drugs
• No concurrent medication for the treatment of hypertension
• No other concurrent investigational drugs
• No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven DuBois

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Childrens Hospital of Orange County

Orange, California, United States

UCSF-Mount Zion

San Francisco, California, United States

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Children's National Medical Center

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

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Countries

United States; Canada

References

Wang E, DuBois SG, Wetmore C, Verschuur AC, Khosravan R. Population Pharmacokinetics of Sunitinib and its Active Metabolite SU012662 in Pediatric Patients with Gastrointestinal Stromal Tumors or Other Solid Tumors. Eur J Drug Metab Pharmacokinet. 2021 May;46(3):343-352. doi: 10.1007/s13318-021-00671-7. Epub 2021 Apr 14.

Reference Type: DERIVED

PMID: 33852135 (View on PubMed)

Wang E, DuBois SG, Wetmore C, Khosravan R. Population pharmacokinetics-pharmacodynamics of sunitinib in pediatric patients with solid tumors. Cancer Chemother Pharmacol. 2020 Aug;86(2):181-192. doi: 10.1007/s00280-020-04106-z. Epub 2020 Jul 4.

Reference Type: DERIVED

PMID: 32623479 (View on PubMed)

Other Identifiers

NCI-2009-00361

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000507414

Identifier Type: -

Identifier Source: secondary_id

COG-ADVL0612

Identifier Type: -

Identifier Source: secondary_id

NCI-07-C-0220

Identifier Type: -

Identifier Source: secondary_id

ADVL0612

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL0612

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00361

Identifier Type: -

Identifier Source: org_study_id