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Childhood Central Nervous System ChoriocarcinomaPhase 1NCT00929903

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

A Phase 1 study testing pazopanib hydrochloride and pharmacological study in people with Childhood Central Nervous System Choriocarcinoma and Childhood Central Nervous System Embryonal Tumor, run by National Cancer Institute (NCI) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 2 to 25 years
What is being tested?
pazopanib hydrochloride and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
14 sitesUnited States
Study dates
Jun 2009to Apr 2013
Phase
Phase 1
Are there results?
None posted in the registry

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 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

None listed.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

About this study

Official title: A Phase I Study of Pazopanib as a Single Agent for Children With Relapsed or Refractory Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
pazopanib hydrochloride, pharmacological study
Medical subject headings
Optic Nerve Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pazopanib hydrochlorideDrug

    Also called GW786034B, Votrient

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00929903
Study groupRoleWhat they receive
Treatment (pazopanib hydrochloride)ExperimentalPatients 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.
Receives: Drug: pazopanib hydrochloride; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose of pazopanib hydrochloride defined as the maximum dose at which fewer that one-third of patients experience DLT

    Graded using the NCI CTCAE version 4.0.

    Measured: 28 days

  2. Adverse events according to NCI CTCAE version 4.0

    Measured: Up to 30 days after completion of study treatment

  3. Pharmacokinetics of pazopanib hydrochloride

    Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Measured: Baseline, days 15, 22, and 27 of course 1 and day 1 of odd courses

Secondary outcomes (1)

  1. Overall response to pazopanib hydrochloride according to RECIST criteria

    The overall response assessment takes into account response in both target and non-target lesions, the appearance of new lesions and normalization of markers.

    Measured: Up to 30 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionApr 2013

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00929903
Sponsor's protocol ID
NCI-2011-01929
Other IDs
NCI-2011-01929, COG-ADVL0815, CDR0000646720, ADVL0815, ADVL0815, U01CA097452
Status last verified
Sep 2013
First submitted
27 Jun 2009
Last updated
30 Sep 2013
Results posted
No

Publications

  • Glade Bender JL, Lee A, Reid JM, Baruchel S, Roberts T, Voss SD, Wu B, Ahern CH, Ingle AM, Harris P, Weigel BJ, Blaney SM. Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children's oncology group phase I consortium report. J Clin Oncol. 2013 Aug 20;31(24):3034-43. doi: 10.1200/JCO.2012.47.0914. Epub 2013 Jul 15.

    PubMed 23857966

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pazopanib hydrochloride and pharmacological study in people with Childhood Central Nervous System Choriocarcinoma and Childhood Central Nervous System Embryonal Tumor, run by National Cancer Institute (NCI) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 87 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00929903, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2013.

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