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Brain TumorsPhase 1/2NCT00107471

Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma

A Phase 1/2 study testing filgrastim, topotecan hydrochloride and radiation therapy in people with Brain Tumors and Central Nervous System Tumors, run by Children's Oncology Group at 80 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 3 to 21 years
Conditions the study is for
Brain Tumors, Central Nervous System Tumors
What is being tested?
filgrastim, topotecan hydrochloride and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
80 sitesin 4 countries
Study dates
Oct 2005to Oct 2007
Phase
Phase 1/2
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 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of intrinsic pontine brain stem glioma within the past 30 days
  • Histologic confirmation not required provided the tumor has a pontine epicenter AND exhibits diffuse (rather than focal) involvement of ≥ 2/3 of the pons with or without extension to the adjacent medulla or midbrain* NOTE: *Brain stem tumors that do not meet these criteria must be histologically confirmed as grade III or IV malignant glioma
  • Measurable disease by radiographic imaging
  • Post-operative MRI required within the past 30 days if patient had a biopsy or surgical resection
  • No disseminated disease
  • No neurofibromatosis type 1

PATIENT CHARACTERISTICS:

Age

  • 3 to 21 at diagnosis

Performance status

  • Lansky 50-100% OR
  • Karnofsky 50-100%

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 2.5 times ULN

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:
  • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
  • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
  • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
  • No greater than 1.5 mg/dL (for patients over 15 years of age)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Not severely somnolent or comatose
  • Central cortical neurotoxicity scale < grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunomodulating agents

Chemotherapy

  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • Concurrent corticosteroids allowed for neurological deficits related to the tumor

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  • Prior biopsy or surgical resection for malignant brain stem glioma allowed

Other

  • No other prior therapy for malignant brain stem glioma

Trial locations and contacts

80 sites in 4 countries.

80 sites in 4 countries

United States72 sites

  • University of New Mexico Cancer Research and Treatment Center

    Albuquerque, New Mexico, 87131-5636

  • Texas Tech University Health Sciences Center School of Medicine - Amarillo

    Amarillo, Texas, 79106

  • C.S. Mott Children's Hospital at University of Michigan Medical Center

    Ann Arbor, Michigan, 48109-0238

  • CancerCare of Maine at Eastern Maine Medial Center

    Bangor, Maine, 04401

  • Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham

    Birmingham, Alabama, 35294

  • St. Luke's Mountain States Tumor Institute - Boise

    Boise, Idaho, 83712-6297

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division

    Charleston, West Virginia, 25302

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195-5217

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • Columbus Children's Hospital

    Columbus, Ohio, 43205-2696

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78466

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Children's Medical Center - Dayton

    Dayton, Ohio, 45404-1815

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Southern California Permanente Medical Group

    Downey, California, 90242-2814

  • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

    Farmington, Connecticut, 06360-2875

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104-9958

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Spectrum Health Hospital - Butterworth Campus

    Grand Rapids, Michigan, 49503-2560

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 95813

  • Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

    Huntington, West Virginia, 25701

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • CCOP - Kalamazoo

    Kalamazoo, Michigan, 49007-5341

  • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

    Kansas City, Kansas, 66160-7357

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada, 89109-2306

  • Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Children's Hospital Central California

    Madera, California, 93638-8762

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota Medical Center & Children's Hospital - Fairview

    Minneapolis, Minnesota, 55455

  • Overlook Hospital

    Morristown, New Jersey, 07962

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6310

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York, 10032

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Florida Hospital Cancer Institute at Florida Hospital Orlando

    Orlando, Florida, 32803-1273

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Sacred Heart Cancer Center at Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Sutter Cancer Center

    Sacramento, California, 95816

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • Providence Cancer Center at Sacred Heart Medical Center

    Spokane, Washington, 99220-2555

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Stanford Comprehensive Cancer Center - Stanford

    Stanford, California, 94305

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • New York Medical College

    Valhalla, New York, 10595

Other trials in United States

Canada4 sites

  • Children's Hospital of Western Ontario

    London, Ontario, N6A 4G5

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

Other trials in Canada

Australia3 sites

  • Royal Children's Hospital

    Herston, Brisbane, Queensland, 4029

  • Women's and Children's Hospital

    North Adelaide, South Australia, 5006

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

Switzerland1 site

  • Swiss Pediatric Oncology Group Bern

    Bern, 3010

Other trials in Switzerland

About this study

Official title: A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Topotecan may make tumor cells more sensitive to radiation therapy . Giving topotecan and G-CSF together with radiation therapy may be an effective treatment for brain stem glioma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of topotecan when given together with G-CSF and radiation therapy and to see how well they work in treating young patients with newly diagnosed brain stem glioma.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the feasibility of escalating the dose of topotecan when administered with filgrastim (G-CSF) and radiotherapy, in terms of increasing the topotecan dose 25-50% above the maximum tolerated dose (MTD) determined in a prior phase I study, in young patients with newly diagnosed malignant intrinsic pontine brain stem glioma. (Phase I)
  • Determine the dose-limiting toxic effects of topotecan in these patients. (Phase I)
  • Determine the 1-year event-free survival and overall survival of patients treated with this regimen (at the MTD of topotecan determined in phase I). (Phase II)
  • Determine the toxicity of this regimen in these patients. (Phase II)

Secondary

  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of topotecan followed by a phase II study.

  • Phase I: Patients receive topotecan IV over 30 minutes followed by radiotherapy once daily, 5 days a week for 6-7 weeks. During chemoradiotherapy, patients also receive filgrastim (G-CSF) IV or subcutaneously daily, if needed, until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 out of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive topotecan (at the MTD determined in phase I ), G-CSF, and radiotherapy as in phase I.

After completion of study treatment, patients are followed within 2 weeks, every 3 months for 1.5 years, every 6 months for 1.5 years, and then annually until disease relapse.

PROJECTED ACCRUAL: A total of 3-72 patients (3-12 for phase I and 60 for phase II) will be accrued for this study within approximately 3 years.

Being tested
filgrastim, topotecan hydrochloride, radiation therapy
Keywords
untreated childhood brain stem glioma
Medical subject headings
Brain Neoplasms, Central Nervous System Neoplasms

What participants receive

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

  • filgrastimBiological

    Also called Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen

    Given PO

  • topotecan hydrochlorideDrug

    Also called SKF-104864, Hycamtin, NSC #609699

    Given IV

  • radiation therapyRadiation

    Also called Conformal therapy or Intensity modulated radiation therapy (IMRT) may be, used.

Study groups in NCT00107471
Study groupRoleWhat they receive
Dose Level I (0.5 mg/m^2)ExperimentalRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
Receives: Biological: filgrastim; Drug: topotecan hydrochloride; Radiation: radiation therapy
Dose Level 2 (0.6 mg/m^2)ExperimentalRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
Receives: Biological: filgrastim; Drug: topotecan hydrochloride; Radiation: radiation therapy

What is being measured

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

  1. Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause)

    Measured: From date of enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death or until last contact if none of these events occur, assessed up to 3 years

Secondary outcomes (1)

  1. Time to death

    Measured: From the time of study entry to the first occurrence of death by any cause

Timeline

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

  1. First posted6 Apr 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionOct 2007

Why it stopped: The unpromising experience of the French group with topotecan given at a dosage of 0.4 mg/m2/day over 30 mins w/in 1 hr of radiation (Cancer 2005; 104: 2792).

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00107471
Sponsor's protocol ID
ACNS0224
Other IDs
CDR0000417842, COG-ACNS0224
Status last verified
Dec 2013
First submitted
5 Apr 2005
Last updated
10 Dec 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing filgrastim, topotecan hydrochloride and radiation therapy in people with Brain Tumors and Central Nervous System Tumors, run by Children's Oncology Group at 80 sites in 4 countries.

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

Who may be eligible to take part?

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: stopped early, as of the sponsor's last update on 10 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, Canada, Australia, Switzerland. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: The unpromising experience of the French group with topotecan given at a dosage of 0.4 mg/m2/day over 30 mins w/in 1 hr of radiation (Cancer 2005; 104: 2792).). Results are not available in the source record.

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?

Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause) (time frame: From date of enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death or until last contact if none of these events occur, assessed up to 3 years). 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 NCT00107471.

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 10 Dec 2013.

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