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

Tracking Information
First Submitted Date ICMJE	June 2, 2005
First Posted Date ICMJE	June 3, 2005
Last Update Posted Date	June 30, 2011
Study Start Date ICMJE	August 2005
Actual Primary Completion Date	August 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 29, 2011)	Estimate the maximum tolerated dose of intraventricular topotecan on this schedule [ Time Frame: First 14 days of therapy ]; Number of patients with dose-limiting toxicity [ Time Frame: First 14 days of therapy ]; 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 [ Time Frame: Day 1 of Week 1 ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00112619 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 29, 2011)	Number of patients with objective documentation of tumor response to intraventricular topotecan [ Time Frame: Weeks 5, 11 and then every 12 weeks until off study ]MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.; Pharmacokinetics [ Time Frame: Day 1 of Week 1 ]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.; Correlation of imaging parameters with tumor response [ Time Frame: Pre-treatment, week 5, week 11, and then every 12 weeks until off study ]MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors
Official Title ICMJE	A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis
Brief 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. 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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Brain and Central Nervous System Tumors; Carcinoma of Unknown Primary; Leukemia; Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific
Intervention ICMJE	Drug: topotecan hydrochloride; 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).; Other Name: Hycamptin
Study Arms	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: June 29, 2011)	19
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	August 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	3 Years to 21 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00112619
Other Study ID Numbers ICMJE	CDR0000430504; U01CA081457 ( U.S. NIH Grant/Contract ); PBTC-019
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	James M. Boyett, Executive Director Operations and Biostatistics Center, Pediatric Brain Tumor Consortium
Study Sponsor ICMJE	Pediatric Brain Tumor Consortium
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Study Chair: Susan M. Blaney, MD Baylor College of Medicine
PRS Account	Pediatric Brain Tumor Consortium
Verification Date	June 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP