DepoCyt Plus Temozolomide in Patients With Neoplastic Meningitis

This study has been terminated.
(Study terminated due to slow accrual with no expansion to additional phase.)
Sponsor:
Collaborators:
Enzon Pharmaceuticals, Inc.
Schering-Plough
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00515788
First received: August 13, 2007
Last updated: March 8, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Neoplastic Meningitis
Drug: DepoCyt
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Temozolomide and Intrathecal DepoCyt in Patients With Neoplastic Meningitis

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) for the combination of Temozolomide and DepoCyt [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 11
Study Start Date: February 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DepoCyt + Temozolomide
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
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).
Other Names:
  • Liposomal Cytarabine
  • Liposomal ara-C
Drug: Temozolomide
100 mg/m^2 (capsules) by mouth daily for 7 consecutive days every 14 days.
Other Name: Temodar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be >/=18 years of age
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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).
  7. 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.
  8. Ventricular access devices (e.g. an Ommaya reservoir) are mandatory.

Exclusion Criteria:

  1. 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.
  2. (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.
  3. 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.
  4. 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.
  5. 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.
  6. 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).
  7. 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.
  8. Patients not able to undergo magnetic resonance testing. i.e. pacemaker.
  9. Patients may not have had prior treatment with Temozolomide.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00515788

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Enzon Pharmaceuticals, Inc.
Schering-Plough
Investigators
Principal Investigator: Morris D. Groves, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00515788     History of Changes
Other Study ID Numbers: 2005-0135
Study First Received: August 13, 2007
Last Updated: March 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Neoplastic Meningitis
Leptomeningeal Disease
Temozolomide
Temodar
DepoCyt
Liposomal Cytarabine
Liposomal ara-C

Additional relevant MeSH terms:
Meningitis
Meningeal Carcinomatosis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Cytarabine
Temozolomide
Dacarbazine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 20, 2014