Neoplastic MeningitisPhase 1PBTC-019NCT00674674

Phase 1 Intrathecal Topotecan for Neoplastic Meningitis

A Phase 1 study testing Topotecan in people with Neoplastic Meningitis, run by Baylor College of Medicine at 1 site in United States.

Completed

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

Official record

Search all trials

Trial summary

1. To find the optimal dose of topotecan that can safely be given directly into the spinal fluid (called intrathecal administration) of children whose cancer has spread to the lining of the brain and/or spinal cord. 2. Read more about this study

Who is it for?: Ages 3 to 21 years
Conditions the study is for: Neoplastic Meningitis
What is being tested?: Topotecan
How many people: 22 participants
Where: 1 siteUnited States
Study dates: Oct 2005to Dec 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

Who may be able to join

Age: Patients must be greater than or equal to 3 years and less than or equal to 21 years of age at study registration.
Diagnosis: Patients must have neoplastic meningitis secondary to an underlying leukemia/lymphoma or a solid tumor (including primary CNS tumors or carcinomas of unknown primary site) for which there is no conventional therapy. Patients with CNS leukemia/lymphoma must be refractory to conventional therapy, including XRT (i.e., 2nd or greater relapse). Neoplastic meningitis is defined as follows: (a)Leukemia/Lymphoma: CSF cell count over 5/µL AND evidence of blast cells on cytospin preparation or by cytology or (b) Solid tumor: Presence of tumor cells on cytospin preparation or cytology OR the unequivocal presence of meningeal disease on MRI scans.
Patients who have leukemia/lymphoma: Patients with CNS leukemia or lymphoma must have a negative bone marrow aspirate assessed within two weeks prior to registration.
Performance Status (Appendix III of full protocol): Karnofsky Performance Scale (KPS for greater than 16 yrs of age) or Lansky Performance Score (LPS for less than or equal to 16 years of age) greater than or equal to 60 assessed within two weeks prior to registration. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purposes of the performance score.
Recovery from Prior Therapy: Patients must have recovered from the acute neurotoxic effects of all prior chemotherapy, biological therapy, immunotherapy, or radiotherapy prior to entering this study and must be without uncontrolled significant systemic illness
5.1 Chemo:

Show all 18Show fewer

Patients must have received their last dose of systemically administered therapy specifically for the treatment of their leptomeningeal disease (must be discussed with study chair) at least three (3) weeks prior to study registration.
Patients must have received their last dose of intrathecal therapy at least one (1) week (2 weeks if intrathecal DepoCyt) prior to study registration.
5.2 XRT: Patients must have had their last fraction of craniospinal irradiation greater than or equal to 8 weeks prior to study registration.
The following laboratory values must be assessed within two (2) weeks prior to registration. Laboratory tests should be repeated within 48 hours of beginning therapy, if there has been a significant clinical change.
6.1 Electrolytes:
Sodium: greater than or equal to 125 and less than or equal to 150 mmol/L
Calcium: greater than or equal to 7 mg/dL
Magnesium: greater than or equal to 0.7 mmol/L
Intraventricular access device: Patients must have or be willing to have an intraventricular access device such as an Ommaya reservoir.
Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to registration. Patient must not be breast-feeding.
Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
Signed informed consent according to institutional guidelines must be obtained.

Who cannot join

CSF Flow: Patients with clinical evidence of obstructive hydrocephalus are not eligible for this protocol. Patients with compartmentalization of CSF flow, as documented by radioisotope Indium111 or Technetium99-DTPA flow study are not eligible for this protocol. Requirement for CSF flow studies are:
1.1 Solid or CNS tumor patients: Nuclear medicine CSF flow studies are required within 7 days prior to registration in all patients with underlying solid or CNS tumors. Informed consent must be obtained prior to the CSF flow study.
1.2 Leukemia or lymphoma patients: Nuclear medicine CSF flow studies are only required if CSF analysis or an MRI suggests that there may be a blockage to CSF flow. The study must be obtained within 7 days prior to registration. Informed consent must be obtained prior to the CSF flow study.
Underlying illness: Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise a patient's ability to tolerate this therapy.
Concomitant Therapy Patients receiving other therapy (either intrathecal or systemic) designed to treat their leptomeningeal disease are not eligible for this study. Note: Patients receiving concomitant chemotherapy to control systemic disease or bulk CNS disease will be eligible, provided that the systemic chemotherapy is not an investigational agent or one of the following: high-dose methotrexate (> 1g/m2), high-dose cytarabine (> 1g/m2), 5-fluorouracil, capecitabine, thiotepa, a nitrosourea, or topotecan. Please discuss plans for systemic therapy with the Study Chair prior to study entry.
Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt are not eligible unless they are completely shunt-independent, e.g., shunts that have an on/off valve that is always in the "off" position.

Show all 10Show fewer

Patients must be free of uncontrolled infection, except HIV patients with AIDS-related lymphomatous meningitis.
Patients currently receiving or who have received an investigational agent within the14 days prior to study registration. The 14 day period should be extended if the investigational agent is known to have delayed toxicity.
Patients with impending spinal cord compression or other CNS involvement requiring emergent local XRT (e.g., acute visual loss secondary to optic nerve involvement).
Patients receiving concomitant radiation therapy to the CNS. Note: Patients may receive radiation therapy to extra-CNS sites, e.g. painful bone metastases not in the craniospinal axis.

Trial locations and contacts

1 site in 1 country.

United States1 site

Texas Children's Hospital
Houston, Texas, 77030

Other trials in United States

About this study

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

To find the optimal dose of topotecan that can safely be given directly into the spinal fluid (called intrathecal administration) of children whose cancer has spread to the lining of the brain and/or spinal cord.
To find out what effects (good and bad) topotecan has when given directly into the cerebrospinal fluid in children with neoplastic meningitis (cancer that has spread to the lining of the brain and spinal cord).

Cerebrospinal fluid is the fluid that circulates around the brain and spinal cord.

To determine if intrathecal topotecan is beneficial to patients.
To better understand how topotecan is handled by the body after intrathecal administration.
To evaluate the cerebrospinal fluid for signs (markers) of tumor spread.

Read the detailed description

This is a multi-center, non-randomized pharmacokinetically-guided optimal dosing study of intraventricular topotecan in children with neoplastic meningitis. Topotecan will be administered daily for five consecutive days utilizing the schema shown in the Schema below. Concomitant chemotherapy to control systemic disease or bulk CNS disease is allowable provided that the systemic chemotherapy is not an investigational agent or one of the following: high-dose methotrexate (> 1g/m2), high-dose cytarabine (> 1g/m2), 5-fluorouracil, capecitabine, thiotepa, a nitrosourea, or topotecan. The starting dose for this trial was derived from pharmacokinetic simulations that utilized data from a prior phase I study of intrathecal topotecan. The simulations were performed to estimate the length of time that ventricular CSF concentrations of topotecan lactone would remain above an optimal "target level" of 1 ng/mL. One of the primary objectives of this study is to estimate the dose of intrathecal topotecan that will result in CSF lactone concentrations exceeding 1 ng/mL for at least eight hours after an intrathecal injection. Dose escalations for patient cohorts will be conducted following the traditional phase 1 design in order to determine the maximum tolerated dose (MTD). The MTD will be called pharmacokinetically optimal if that dose achieves the targeted PK parameter in at least 23 of 25 patients treated at that dose level.

Conditions: Neoplastic Meningitis
Being tested: Topotecan
Keywords: topotecan, pharmacokinetics, neoplastic, meningitis
Medical subject headings: Meningeal Carcinomatosis, Meningitis

What participants receive

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

TopotecanDrug
Induction (4 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 3.
The Induction period is the first 4 weeks of therapy.
TopotecanDrug
Consolidation (6 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 4. The Consolidation period is 6 weeks in duration. Consolidation begins immediately after completion of the 4th week of Induction.
TopotecanDrug
Maintenance (4 weeks for 11 courses): Patients will receive IT topotecan for 5 consecutive days during week 1. Each course of Maintenance is 4 weeks in duration. Maintenance begins immediately after completion of the 6th week of Consolidation.

What is being measured

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

To estimate the MTD of intrathecal topotecan administered daily for 5 consecutive days.
Measured: 14 days
To describe the toxicities and define the dose-limiting toxicity of intrathecally administered topotecan following intraventricular administration daily for 5 consecutive days.
Measured: 30 days
To determine if the MTD of intrathecal topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF.
Measured: 7 days

Secondary outcomes (4)

To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial.
Measured: 2 years
To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intrathecal topotecan.
Measured: 2 years
To further describe the CSF pharmacokinetics of topotecan following intrathecal administration.
Measured: 2 years
To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intrathecal therapy.
Measured: 2 years

Timeline

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

Oct 2005Dec 2010

First posted8 May 2008 (estimated)
Study startOct 2005
Primary completionAug 2010
Study completionDec 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Neoplastic MeningitisStudies of the same condition, open and under way.
More trials run by Baylor College of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Supportive care
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00674674
Sponsor's protocol ID: H-17990
Other IDs: PBTC-019
Acronym: PBTC-019
Status last verified: May 2012
First submitted: 21 Dec 2007
Last updated: 15 May 2012
Results posted: No
Data monitoring committee: Yes

Publications

Potter SL, Berg S, Ingle AM, Krailo M, Adamson PC, Blaney SM. Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: a Children's Oncology Group trial (P9962). Pediatr Blood Cancer. 2012 Mar;58(3):362-5. doi: 10.1002/pbc.23317. Epub 2011 Sep 9.
PubMed 21910214

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Multiple Dose Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases
Leptomeningeal Metastasis
Active, not recruitingObservational study
SERS-Based Diagnosis of Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Lung Adenocarcinoma EGFR-mutated, Leptomeningeal Metastasis From Lung Cancer
Recruiting
Tumor Treating Fields for the Treatment of Leptomeningeal Metastases of the Spine in Patients With Breast or Lung Cancer
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis
Metastatic Breast Cancer, Leptomeningeal Disease

All Neoplastic Meningitis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Pharmacokinetic Optimal Dosing Study of Intrathecal Topotecan for Children With Neoplastic Meningitis
ClinicalTrials.gov ID: NCT00674674
Acronym / sponsor ID: PBTC-019 / H-17990
Conditions: Neoplastic Meningitis
Keywords: topotecan, pharmacokinetics, neoplastic, meningitis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Baylor College of MedicineUniversity, hospital or other
Collaborators: GlaxoSmithKline
Study start: Oct 2005
Primary completion: Aug 2010 (actual)
Study completion: Dec 2010 (actual)
First posted: 8 May 2008 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To find the optimal dose of topotecan that can safely be given directly into the spinal fluid (called intrathecal administration) of children whose cancer has spread to the lining of the brain and/or spinal cord.
To find out what effects (good and bad) topotecan has when given directly into the cerebrospinal fluid in children with neoplastic meningitis (cancer that has spread to the lining of the brain and spinal cord).

Cerebrospinal fluid is the fluid that circulates around the brain and spinal cord.

To determine if intrathecal topotecan is beneficial to patients.
To better understand how topotecan is handled by the body after intrathecal administration.
To evaluate the cerebrospinal fluid for signs (markers) of tumor spread.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 3 to 21 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (18 listed)

Age: Patients must be greater than or equal to 3 years and less than or equal to 21 years of age at study registration.
Diagnosis: Patients must have neoplastic meningitis secondary to an underlying leukemia/lymphoma or a solid tumor (including primary CNS tumors or carcinomas of unknown primary site) for which there is no conventional therapy. Patients with CNS leukemia/lymphoma must be refractory to conventional therapy, including XRT (i.e., 2nd or greater relapse). Neoplastic meningitis is defined as follows: (a)Leukemia/Lymphoma: CSF cell count over 5/µL AND evidence of blast cells on cytospin preparation or by cytology or (b) Solid tumor: Presence of tumor cells on cytospin preparation or cytology OR the unequivocal presence of meningeal disease on MRI scans.
Patients who have leukemia/lymphoma: Patients with CNS leukemia or lymphoma must have a negative bone marrow aspirate assessed within two weeks prior to registration.
Performance Status (Appendix III of full protocol): Karnofsky Performance Scale (KPS for greater than 16 yrs of age) or Lansky Performance Score (LPS for less than or equal to 16 years of age) greater than or equal to 60 assessed within two weeks prior to registration. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purposes of the performance score.
Recovery from Prior Therapy: Patients must have recovered from the acute neurotoxic effects of all prior chemotherapy, biological therapy, immunotherapy, or radiotherapy prior to entering this study and must be without uncontrolled significant systemic illness

Key exclusion criteria (10 listed)

CSF Flow: Patients with clinical evidence of obstructive hydrocephalus are not eligible for this protocol. Patients with compartmentalization of CSF flow, as documented by radioisotope Indium111 or Technetium99-DTPA flow study are not eligible for this protocol. Requirement for CSF flow studies are:
1.1 Solid or CNS tumor patients: Nuclear medicine CSF flow studies are required within 7 days prior to registration in all patients with underlying solid or CNS tumors. Informed consent must be obtained prior to the CSF flow study.
1.2 Leukemia or lymphoma patients: Nuclear medicine CSF flow studies are only required if CSF analysis or an MRI suggests that there may be a blockage to CSF flow. The study must be obtained within 7 days prior to registration. Informed consent must be obtained prior to the CSF flow study.
Underlying illness: Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise a patient's ability to tolerate this therapy.
Concomitant Therapy Patients receiving other therapy (either intrathecal or systemic) designed to treat their leptomeningeal disease are not eligible for this study. Note: Patients receiving concomitant chemotherapy to control systemic disease or bulk CNS disease will be eligible, provided that the systemic chemotherapy is not an investigational agent or one of the following: high-dose methotrexate (> 1g/m2), high-dose cytarabine (> 1g/m2), 5-fluorouracil, capecitabine, thiotepa, a nitrosourea, or topotecan. Please discuss plans for systemic therapy with the Study Chair prior to study entry.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TopotecanInduction (4 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 3. The Induction period is the first 4 weeks of therapy.	Drug	–
TopotecanConsolidation (6 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 4. The Consolidation period is 6 weeks in duration. Consolidation begins immediately after completion of the 4th week of Induction.	Drug	–
TopotecanMaintenance (4 weeks for 11 courses): Patients will receive IT topotecan for 5 consecutive days during week 1. Each course of Maintenance is 4 weeks in duration. Maintenance begins immediately after completion of the 6th week of Consolidation.	Drug	–

Primary outcome

To estimate the MTD of intrathecal topotecan administered daily for 5 consecutive days.
Time frame: 14 days
To describe the toxicities and define the dose-limiting toxicity of intrathecally administered topotecan following intraventricular administration daily for 5 consecutive days.
Time frame: 30 days
To determine if the MTD of intrathecal topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF.
Time frame: 7 days

4 secondary outcomes

To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial.
Time frame: 2 years
To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intrathecal topotecan.
Time frame: 2 years
To further describe the CSF pharmacokinetics of topotecan following intrathecal administration.
Time frame: 2 years
To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intrathecal therapy.
Time frame: 2 years

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2012.
Results publication: PubMed 21910214Potter SL, Berg S, Ingle AM, Krailo M, Adamson PC, Blaney SM. Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: a Children's Oncology Group trial (P9962). Pediatr Blood Cancer. 2012 Mar;58(3):362-5. doi: 10.1002/pbc.23317. Epub 2011 Sep 9.

Related trials for Neoplastic Meningitis

RecruitingPhase 1/2
Multiple Dose Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases
Leptomeningeal Metastasis
Active, not recruitingObservational study
SERS-Based Diagnosis of Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Lung Adenocarcinoma EGFR-mutated, Leptomeningeal Metastasis From Lung Cancer
Recruiting
Tumor Treating Fields for the Treatment of Leptomeningeal Metastases of the Spine in Patients With Breast or Lung Cancer
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis
Metastatic Breast Cancer, Leptomeningeal Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Susan Blaney, MD principal investigator

Baylor College of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Topotecan in people with Neoplastic Meningitis, run by Baylor College of Medicine at 1 site 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 18 inclusion and 10 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 15 May 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

To estimate the MTD of intrathecal topotecan administered daily for 5 consecutive days. (time frame: 14 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 NCT00674674, 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 15 May 2012.