DepoCyt Plus Temozolomide in Patients With Neoplastic Meningitis

NCT00515788 | Terminated Phase 1

• 1 other identifier: 2005-0135
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: \- To determine the safety, tolerability and maximum tolerated dose (MTD) of oral temozolomide using a 7 days on and 7 days off regimen combined with intrathecal liposomal cytarabine (DepoCyt) in patients with neoplastic meningitis from solid tumors and systemic lymphoma.

Conditions

Neoplastic Meningitis

Keywords

Neoplastic Meningitis; Leptomeningeal Disease; Temozolomide; Temodar; DepoCyt; Liposomal Cytarabine; Liposomal ara-C

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) for the combination of Temozolomide and DepoCyt

  The MTD is the dose at which 0/3 or 1/6 participants experience Dose Limiting Toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 participants encountering DLT. MTD based on the assessment of DLT during the first 28 days of treatment on the regimen.

  28 days

Study Arms (1)

DepoCyt + Temozolomide

EXPERIMENTAL

DepoCyt Starting 50 mg Intrathecal Day 1 every 14 days for 12 weeks (6 treatments), then every 28 days for 40 weeks (10 treatments). Temozolomide 100 mg/m\^2 by mouth daily for 7 days every 14 days.

Drug: DepoCyt; Drug: Temozolomide

Interventions

DepoCyt DRUG

Starting dose of 50 mg Intrathecal on Day 1 every 14 days for a total of 12 weeks (6 treatments). After the first 12 weeks, 50 mg Intrathecal on Day 1 every 28 days for 40 weeks (10 treatments).

Also known as: Liposomal Cytarabine, Liposomal ara-C

DepoCyt + Temozolomide

Temozolomide DRUG

100 mg/m\^2 (capsules) by mouth daily for 7 consecutive days every 14 days.

Also known as: Temodar

DepoCyt + Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be \>/=18 years of age
• All patients with the exception of those with primary brain tumors, must have histologic diagnosis of systemic malignancy. Patients must have the presence of malignant cells in CSF (+CSF) or clinical signs and symptoms of leptomeningeal disease and radiographic abnormalities without malignant cells identified in the CSF (-CSF). Clinical signs/symptoms include cerebral hemispheric, cranial nerve, and/or spinal cord/root dysfunction.
• Patients must have Karnofsky performance status of \>/=60%. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purposes of the performance score.
• Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, before entering the study and must be without significant systemic illness. Patients must not have received any systemic therapy for Leptomeningeal disease (LMD) within 3 wks (6 wks if a nitrosourea), intrathecal chemotherapy within 1 wk, or irradiation within 8 wks prior to treatment on this study. Patients previously receiving craniospinal irradiation must have positive cytology or progression of meningeal disease on MRI scan. Patients must not have received whole brain or focal CNS radiotherapy within 1 wk of treatment.
• Patients must have a platelet count \>/= 75,000/mm(3) and ANC \>/= 1500/mm(3) within 72 hours prior to intrathecal DepoCyt and temozolomide treatment.
• Patients must have adequate liver function, total bilirubin \< 2.0 mg%; SGPT \< 5 times normal; adequate renal function (serum creatinine \</= 1.5 mg); and normal metabolic parameters (serum electrolytes, calcium, magnesium, and phosphorus).
• All patients or their legal guardians must sign a document of informed consent indicating their awareness of the investigational nature and the risks of this study.
• Ventricular access devices (e.g. an Ommaya reservoir) are mandatory.

You may not qualify if:

• Patients receiving other therapy (either intrathecal or systemic) designed specifically to treat their leptomeningeal disease are not eligible for this study. However, patients receiving concomitant non-cytotoxic therapy (hormonal or cytostatic therapy) to control systemic disease or bulk CNS disease will be eligible, provided the therapy is not a phase I agent, an agent which significantly penetrates the CSF or an agent known to have serious unpredictable CNS side effects.
• (1. continued) No other cytotoxic chemotherapies are allowed (non-cytotoxic therapies such as herceptin, tarceva, arimidex etc are allowed at the investigator's discretion). Careful documentation of concurrently administered systemic drugs is required.
• Patients with clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by radioisotope Indium-(111) (Technetium(99) -DTPA when Indium-(111) unavailable) flow study are not eligible for this protocol. CSF obstruction will be determined by routine nuclear medicine CSF flow study parameters. If patients have evidence of block that is subsequently proven to be relieved after focal XRT, these patients can enroll immediately after repeat flow study shows block to be relieved.
• Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt must have an on/off device in their shunt systems to be eligible for the study. Patients must be able to tolerate shunt closure for \>/= 4 hours without development of clinical signs of increased intracranial pressure. Patients unable to tolerate shunt closure for \>/= 4 hours will not be eligible for the study.
• Women of childbearing potential (females who are not surgically sterile or who have had a period in the last 12 months) must have a negative serum pregnancy test and must not be lactating.
• Patients with any uncontrolled infection (life-threatening infection resistant to treatment after 7 days) are not eligible for this study, except those with HIV and AIDS-related lymphomatous meningitis).
• Use of any other investigational drug within 7 days prior to study entry. This period should be extended if the patient has received any investigational agent that is known to have delayed toxicities after 7 days or a prolonged half-life.
• Patients not able to undergo magnetic resonance testing. i.e. pacemaker.
• Patients may not have had prior treatment with Temozolomide.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Enzon Pharmaceuticals, Inc.: collaborator
• Schering-Plough: collaborator

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Meningeal Carcinomatosis; Meningeal Neoplasms

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Morris D. Groves, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2007
• First Posted: August 14, 2007
• Study Start: February 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 12, 2012

Record last verified: 2012-03

Locations

US (1)