Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Relapsed or Not Responded to Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00929903
First received: June 27, 2009
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

This phase I trial is studying the side effects and best dose of pazopanib hydrochloride in treating young patients with solid tumors that have relapsed or not responded to treatment. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
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
Metastatic Childhood Soft Tissue Sarcoma
Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Central Nervous System Embryonal Tumor
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Childhood Visual Pathway Glioma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: pazopanib hydrochloride
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Pazopanib as a Single Agent for Children With Relapsed or Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose of pazopanib hydrochloride defined as the maximum dose at which fewer that one-third of patients experience DLT [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Graded using the NCI CTCAE version 4.0.

  • Adverse events according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of pazopanib hydrochloride [ Time Frame: Baseline, days 15, 22, and 27 of course 1 and day 1 of odd courses ] [ Designated as safety issue: No ]
    Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Secondary Outcome Measures:
  • Overall response to pazopanib hydrochloride according to RECIST criteria [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    The overall response assessment takes into account response in both target and non-target lesions, the appearance of new lesions and normalization of markers.


Enrollment: 55
Study Start Date: June 2009
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Given orally
Other Names:
  • GW786034B
  • Votrient
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Estimate the maximum-tolerated dose and/or recommended phase II dose of pazopanib hydrochloride in pediatric patients with relapsed or refractory solid tumors.

II. Define and describe the toxicities of this regimen in these patients. III. Characterize the pharmacokinetics of pazopanib hydrochloride in these patients.

SECONDARY OBJECTIVES:

I. Preliminarily define the antitumor activity of pazopanib hydrochloride within the confines of a phase I study.

II. Evaluate changes in tumor vascular permeability following initiation of pazopanib hydrochloride and correlate these changes with clinical outcome by dynamic contrast-enhanced MRI.

OUTLINE: This is a multicenter study dose-escalation study.

Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients accrued after the maximum-tolerated dose (MTD) of pazopanib hydrochloride has been determined receive pazopanib hydrochloride as an oral suspension.

Some patients undergo dynamic contrast-enhanced MRI at baseline and periodically during study. Blood samples are collected at baseline and periodically during study for pharmacokinetic studies.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:

NOTE: Histologic confirmation not required for intrinsic brain stem cell tumor, optic pathway gliomas, pineal tumors and elevations of cerebrospinal fluid, and serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin.

  • Histologically confirmed relapsed or refractory solid tumors at original diagnosis including CNS tumors* (Part 1 and Part 2a)

    • Neurologic deficits in patients with CNS tumors must have been relatively stable for ≥ 1 week
  • Histologically confirmed soft tissue sarcoma, desmoplastic small round cell tumor, or extraosseus Ewing sarcoma at original diagnosis including the following (Part 2b):

    • Tumor in the head, neck, or extremity or fixed within the abdomen or pelvis that it is not sensitive to motion artifact
    • No isolated pulmonary metastases

      • Disease with no known curative therapy or no therapy proven to prolong survival with acceptable quality of life
      • Measurable or evaluable disease (Part 1 and Part 2a)
      • Measurable tumor that is ≥ 2 cm in its longest diameter (Part 2b)
      • Patients must be:
  • > 2 years of age and ≤ 21 years of age (Part 1 and Part 2a)
  • > 2 years of age and ≤ 25 years of age (Part 2b)

    • Body surface area ≥ 0.48 m^2 (Part 1 and Part 2b)
    • For patients with CNS tumors or CNS metastasis, there must be no evidence of new CNS hemorrhage of more than punctate size and/or > 3 foci of punctate hemorrhage on baseline MRI for primary CNS tumors ≥ 14 days prior to study entry
    • Karnofsky performance status (PS) 50-100% (> 16 years of age)
    • Lansky PS 50-100% (≤ 16 years of age)
    • Platelet count ≥ 100,000/mm^3 (transfusion independent)
    • ANC ≥ 1,000/mm^3
    • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
    • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
  • 0.6 mg/dL (1 to < 2 years of age)
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 mg/dL (male ) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • 1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)

    • Urine protein:creatinine ratio < 1 OR urinalysis negative for protein OR 24-hour urine protein level < 1 g
    • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
    • ALT ≤ 110 U/L
    • PT and PTT ≤ 1.2 times ULN
    • INR ≤ 1.2
    • Serum albumin ≥ 2 g/dL
    • No grade > 1 abnormalities of potassium, calcium, magnesium, or phosphorous
  • Supplementation allowed

    • Not pregnant or nursing
    • Negative pregnancy test
    • Fertile patients must use effective contraception
  • Oral contraceptives are not considered effective

    • Adequate cardiac function defined as any of the following:
  • Shortening fraction of ≥ 27% by echocardiogram
  • Ejection fraction of ≥ 50% by gated radionuclide study
  • QTc < 450 msec
  • No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease or familial QTc prolongation

    • Adequate blood pressure defined as ≤ 95th percentile for age, height, and gender
    • Known history of well-controlled seizures allowed
    • Able to swallow whole tablets (Part 1 and Part 2b)
    • No uncontrolled infection
    • No evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis
    • None of the following conditions within the past 6 months:
  • Arterial thromboembolic events, including transient ischemic attack or cerebrovascular accident
  • Pulmonary embolism
  • Deep vein thrombosis
  • Other venous thromboembolic event

    • No hemoptysis within the past 6 weeks
    • No serious or non-healing wound, ulcer, or bone fracture
    • No significant traumatic injury within the past 28 days
    • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
    • No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
    • No fine-needle aspiration within 48 hours before day 1 of therapy
    • Fully recovered from all prior therapy (e.g., chemotherapy, immunotherapy, or radiotherapy)
    • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for prior nitrosourea)
    • At least 7 days since prior hematopoietic growth factor
    • At least 21 days since prior VEGF-Trap
    • No prior pazopanib hydrochloride
    • At least 7 days since prior VEGF-blocking tyrosine kinase inhibitor or other biological agents
    • At least 3 half-lives since prior monoclonal antibody, including bevacizumab
    • At least 21 days since any other prior anticancer antibody therapy
    • At least 2 weeks since prior local palliative radiotherapy (small port)
    • At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or ≥ 50% radiotherapy to the pelvis
    • At least 6 weeks since prior other substantial bone marrow radiotherapy
    • At least 2 months since stem cell transplantation and no evidence of graft-vs-host disease
    • Thyroid replacement therapy allowed provided a stable dose has been received for ≥ 4 weeks
    • No concurrent medication for cardiac function or hypertension
    • Concurrent corticosteroids allowed provided dose is stable or decreasing for > 7 days (for patients enrolled in Part 1 and Part 2a of study)
  • No concurrent corticosteroids for patients enrolled in Part 2b of the study

    • No other concurrent anticancer agents or radiotherapy
    • No other concurrent investigational drugs
    • No concurrent enzyme-inducing anticonvulsants
    • No concurrent anticoagulation therapy with coumadin and/or low molecular weight heparin
  • Prophylactic anticoagulation therapy (i.e., intraluminal heparin) of venous or arterial access devices allowed

    • No concurrent aspirin, ibuprofen, or other NSAIDs
    • No concurrent drugs metabolized through several of the specific P450 cytochrome isoform including inducers or inhibitors of CYP3A4
    • No concurrent drugs with a known risk of torsades de pointes
    • At least 28 days since prior major surgical procedure, laparoscopic procedure, or open biopsy
  • Port placement or central line placement 48 hours before day 1 of therapy allowed

    • No core biopsy within the past 7 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00929903

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Principal Investigator: Julia Glade-Bender COG Phase I Consortium
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00929903     History of Changes
Other Study ID Numbers: NCI-2011-01929, NCI-2011-01929, COG-ADVL0815, CDR0000646720, ADVL0815, ADVL0815, U01CA097452
Study First Received: June 27, 2009
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sarcoma
Glioma
Neoplasms, Germ Cell and Embryonal
Endodermal Sinus Tumor
Choriocarcinoma
Optic Nerve Glioma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Mesonephroma
Trophoblastic Neoplasms
Gestational Trophoblastic Disease
Adenocarcinoma
Carcinoma
Pregnancy Complications, Neoplastic
Pregnancy Complications
Astrocytoma
Optic Nerve Neoplasms
Cranial Nerve Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Peripheral Nervous System Neoplasms
Cranial Nerve Diseases
Nervous System Diseases
Optic Nerve Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 29, 2014