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Brain and Central Nervous System TumorsPhase 1NCT00112619

Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors

A Phase 1 study testing topotecan hydrochloride in people with Brain and Central Nervous System Tumors and Carcinoma of Unknown Primary, run by Pediatric Brain Tumor Consortium at 11 sites in United States.

Terminated

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

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer 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
What is being tested?
topotecan hydrochloride
How many people
19 participants
Where
11 sitesUnited States
Study dates
Aug 2005to Aug 2010
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 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of neoplastic meningitis secondary to leukemia, lymphoma (including AIDS-related lymphoma), or solid tumor (including primary CNS tumors or carcinomas of unknown primary site), defined by 1 of the following criteria:
  • Cerebral spinal fluid (CSF) cell count > 5/μL AND evidence of blast cells on cytospin or by cytology (for patients with leukemia or lymphoma)
  • Presence of tumor cells on cytospin or cytology OR unequivocal presence of meningeal disease by MRI (for patients with solid tumor)
  • No conventional therapy for neoplastic meningitis exists
  • Patients with CNS leukemia or lymphoma must be refractory to conventional therapy, including radiotherapy (i.e., second or greater relapse)
  • Patients with CNS leukemia or lymphoma must have had a negative bone marrow aspiration within the past 2 weeks
  • No clinical evidence of obstructive hydrocephalus
  • No compartmentalization of CSF flow by radioisotope indium In 111 or technetium Tc 99 DTPA flow study
  • No ventriculoperitoneal or ventriculoatrial shunt unless patient is completely shunt-independent
  • No impending spinal cord compression or other CNS involvement (e.g., acute visual loss secondary to optic nerve involvement) requiring emergent local radiotherapy

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

  • Lansky 60-100% (≤ 16 years of age) OR
  • Karnofsky 60-100% (> 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Calcium ≥ 7 mg/dL

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Sodium 125-150 mmol/L
  • Magnesium ≥ 0.7 mmol/L
  • Must have or be willing to have an intraventricular access device (i.e., Ommaya reservoir)
  • No uncontrolled infection
  • HIV-positive patients with AIDS-related lymphomatous meningitis are eligible
  • No other significant uncontrolled systemic medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Recovered from prior biologic therapy or immunotherapy

Chemotherapy

  • Recovered from prior chemotherapy
  • At least 1 week since prior intra-colony stimulating factory (CSF) chemotherapy (2 weeks for liposomal cytarabine)
  • At least 3 weeks since prior systemic chemotherapy for leptomeningeal disease
  • Concurrent systemic chemotherapy to control systemic disease or bulk CNS disease allowed provided the systemic chemotherapy is not an investigational agent OR any of the following:
  • High-dose (> 1 g/m^2) methotrexate
  • High-dose (> 1 g/m^2) cytarabine
  • Fluorouracil
  • Capecitabine
  • Thiotepa
  • Nitrosoureas
  • Topotecan

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • At least 8 weeks since prior craniospinal radiotherapy and recovered
  • No concurrent CNS radiotherapy
  • Concurrent radiotherapy to extra-CNS sites (e.g., painful bone metastases not in the craniospinal axis) allowed

Surgery

  • Not specified

Other

  • More than 2 weeks since prior and no other concurrent investigational agents
  • No other concurrent intra-CSF or systemic therapy for leptomeningeal disease

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

    Bethesda, Maryland, 20892-1182

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

    Boston, Massachusetts, 02115

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Dan L. Duncan Cancer Center at Baylor College of Medicine

    Houston, Texas, 77030

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-4318

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

About this study

Official title: A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis

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

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of intraventricular topotecan in young patients with neoplastic meningitis secondary to leukemia, lymphoma, or solid tumors.
  • Determine the toxic effects and dose-limiting toxicity of this drug in these patients.
  • Determine whether the MTD of this drug is also the pharmacokinetic optimal dose, defined by the topotecan lactone concentration in the cerebral spinal fluid (CSF), in these patients.

Secondary

  • Determine, preliminarily, the antitumor activity of this drug in these patients.
  • Determine the pharmacokinetics of this drug in the CSF of these patients.
  • Correlate observed effects of post-treatment central review imaging (if feasible) with response to this drug in these patients.

OUTLINE: This is a non-randomized, dose-escalation, multicenter study.

  • Induction therapy (weeks 1-4): Patients receive topotecan intraventricularly* over 5 minutes on days 1-5 in weeks 1 and 3. Patients then proceed to consolidation therapy in week 5.

NOTE: *Patients who are willing, receive 1 intralumbar (instead of intraventricular) dose of topotecan on day 1 of week 3 only.

  • Consolidation therapy (weeks 5-10): Patients receive topotecan intraventricularly on days 1-5 in weeks 5 and 8. Patients then proceed to maintenance therapy in week 11.
  • Maintenance therapy (weeks 11-54): Patients receive topotecan intraventricularly on days 1-5 in weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51.

Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan until the maximum tolerated dose (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.

Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the target pharmacokinetic parameter.

PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24 months.

Being tested
topotecan hydrochloride
Keywords
AIDS-related diffuse large cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related lymphoblastic lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, AIDS-related small noncleaved cell lymphoma, HIV-associated Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, stage IV childhood large cell lymphoma, stage IV childhood lymphoblastic lymphoma, stage IV childhood small noncleaved cell lymphoma, primary central nervous system non-Hodgkin lymphoma, primary central nervous system Hodgkin lymphoma, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, unspecified childhood solid tumor, protocol specific, childhood grade I meningioma, childhood grade II meningioma
Medical subject headings
Central Nervous System Neoplasms, Neoplasms, Unknown Primary, Leukemia, Lymphoma, Dendritic Cell Sarcoma, Interdigitating, Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Astrocytoma

What participants receive

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

  • topotecan hydrochlorideDrug

    Also called Hycamptin

    Participants receive intraventricular topotecan, .2 mg, administered via an indwelling ventricular reservoir daily for 5 consecutive days during weeks 1 and 3 of the first four weeks of therapy (induction), during weeks 5 and 8 of the next 6 weeks of therapy (consolidation), and during weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51 (maintenance therapy).

What is being measured

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

  1. Estimate the maximum tolerated dose of intraventricular topotecan on this schedule

    Measured: First 14 days of therapy

  2. Number of patients with dose-limiting toxicity

    Measured: First 14 days of therapy

  3. Estimate the dose of intraventricular topotecan that will result in cerebrospinal fluid lactone concentrations exceeding 1 ng/mL for at least 8 hours after an intrathecal injection

    Measured: Day 1 of Week 1

Secondary outcomes (3)

  1. Number of patients with objective documentation of tumor response to intraventricular topotecan

    MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.

    Measured: Weeks 5, 11 and then every 12 weeks until off study

  2. Pharmacokinetics

    The cerebrospinal fluid (CSF) concentration-time profile for topotecan after intrathecal CSF administration will be modeled from the CSF samples collected on day 1 of week 1. Individual pharmacokinetic parameters estimated will include volume of central compartment, elimination rate constant, half-life, and clearance.

    Measured: Day 1 of Week 1

  3. Correlation of imaging parameters with tumor response

    MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.

    Measured: Pre-treatment, week 5, week 11, and then every 12 weeks until off study

Timeline

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

  1. First posted3 Jun 2005 (estimated)
  2. Study startAug 2005
  3. Primary completionAug 2010

Why it stopped: Slow accrual and company withdrawing support to supply the drug

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00112619
Sponsor's protocol ID
CDR0000430504
Other IDs
U01CA081457, PBTC-019
Status last verified
Jun 2011
First submitted
2 Jun 2005
Last updated
30 Jun 2011
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing topotecan hydrochloride in people with Brain and Central Nervous System Tumors and Carcinoma of Unknown Primary, run by Pediatric Brain Tumor Consortium at 11 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?

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 30 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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 was stopped early (reason given: Slow accrual and company withdrawing support to supply the drug). 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?

Estimate the maximum tolerated dose of intraventricular topotecan on this schedule (time frame: First 14 days of therapy). 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 NCT00112619.

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 Jun 2011.

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