Phase 1 Intrathecal Topotecan for Neoplastic Meningitis

NCT00674674 | Completed Phase 1 DMC

• 2 other identifiers: H-17990PBTC-019
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 2.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).
3. 3.Cerebrospinal fluid is the fluid that circulates around the brain and spinal cord.
4. 4.To determine if intrathecal topotecan is beneficial to patients.
5. 5.To better understand how topotecan is handled by the body after intrathecal administration.
6. 6.To evaluate the cerebrospinal fluid for signs (markers) of tumor spread.

Conditions

Neoplastic Meningitis

Keywords

topotecan; pharmacokinetics; neoplastic; meningitis

Outcome Measures

Primary Outcomes (3)

• To estimate the MTD of intrathecal topotecan administered daily for 5 consecutive days.

  14 days

• To describe the toxicities and define the dose-limiting toxicity of intrathecally administered topotecan following intraventricular administration daily for 5 consecutive days.

  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.

  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.

  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.

  2 years

• To further describe the CSF pharmacokinetics of topotecan following intrathecal administration.

  2 years

• To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intrathecal therapy.

  2 years

Interventions

Topotecan DRUG

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.

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Chemo:
• 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.
• 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.
• 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.

You may not qualify if:

• 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:
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 21910214 RESULT

MeSH Terms

Conditions

Meningeal Carcinomatosis; Meningitis

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Susan Blaney, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: May 8, 2008
• Study Start: October 1, 2005
• Primary Completion: August 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 15, 2012

Record last verified: 2012-05

Locations

US (1)