Study to Demonstrate the Safety of WBR Administered at the Same Time as Intrathecal Liposomal Cytarabine (DepoCyte®) Versus Intrathecal Liposomal Cytarabine (DepoCyte®) Administered After WBR for the Treatment of Solid Tumour Neoplastic Meningitis in Patients With or Without Brain Metastasis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mundipharma Research Limited
ClinicalTrials.gov Identifier:
NCT00854867
First received: March 2, 2009
Last updated: February 21, 2014
Last verified: February 2013
  Purpose

The purpose of this study is to demonstrate the safety of giving Whole Brain Radiotherapy (WBRT) together with intrathecal liposomal cytarabine (DepoCyte®) for patients with leptomeningeal metastases. The study will compare the safety of giving DepoCyte at the same time as WBRT with giving the drug after WBRT is complete.


Condition Intervention Phase
Solid Tumour Neoplastic Meningitis
Brain Metastases
Drug: Whole Brain Radio Therapy (WBRT) with sequential Depocyte
Drug: Whole brain radiotherapy (WBRT) with concomitant Depocyte
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Randomised Multi-centre Study to Demonstrate the Safety of WBRT Concomitant to Intrathecal Liposomal Cytarabine (DepoCyte®) Versus WBRT & Sequential Intrathecal Liposomal Cytarabine (DepoCyte®) for Treatment of STNM With or Without Brain Metastasis.

Resource links provided by NLM:


Further study details as provided by Mundipharma Research Limited:

Primary Outcome Measures:
  • To demonstrate that WBRT concomitant to DepoCyte is as safe as WBRT & sequential DepoCyte in treating solid tumour neoplastic meningitis with/without brain metastasis. [ Time Frame: Safety is reviewed at every visit & for 3 months after last Depocyte administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Safety is reviewed at every visit & for 3 months after last Depocyte administration ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: Safety is reviewed at every visit & for 3 months after last Depocyte administration ] [ Designated as safety issue: No ]
  • Time to neurologial progression (TNP) [ Time Frame: Safety is reviewed at every visit & for 3 months after last Depocyte administration ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Safety is reviewed at every visit & for 3 months after last Depocyte administration ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: February 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Whole brain radiotherapy (WBRT) with concomitant Depocyte
Subjects will receive a total of 38.4 Gray (Gy) WBRT given over 4 weeks. Subjects will receive 3 GyWBRT on Days 1 and 2 and then 1.8 Gy on the third fourth and fifth days of WBRT treatment during Week 1. Subjects will then receive 1.8 Gy WBRT per day; 5 days out of seven, each week for the next 3 weeks. A total of 4 doses of DepoCyte (50 mg of liposomal ARA-C) will be administered intrathecally. The first dose will be administered on Day 3 (or Day 4 or 5) of Week 1, i.e. the third day of radiotherapy treatment when the dosage is reduced to 1.8 Gy. The second dose will be administered on Day 17(+2 days); the third dose will be administered on Day 31 (+2 days); the fourth dose will be administered on Day 45 (+2 days) to complete the induction phase of the protocol. Subjects will continue to receive an additional 6 doses of DepoCyte one dose every 28 days (+2 days) during the maintenance period. The first dose will be given 28 days after the last dose in the induction phase.
Drug: Whole brain radiotherapy (WBRT) with concomitant Depocyte
Active Comparator: Whole Brain Radio Therapy (WBRT) with sequential Depocyte
Subjects will receive a total of 38.4 Gy WBRT given over 4 weeks. Subjects will receive 3 Gy (WBRT on Day 1 and Day 2) and then 1.8 Gy on the third fourth and fifth days of WBRT treatment during Week 1. Subjects will then receive 1.8 Gy WBRT per day; 5 days out of seven, each week for the next 3 weeks. A total of 4 doses of DepoCyte (50 mg of liposomal ARA-C) will be administered intrathecally. The first dose will be administered on Day 29 (+2 days); the second dose will be administered on Day 43(+2 days); the third dose will be administered on Day 57 (+2 days); the fourth dose will be administered on Day 71 (+2 days) to complete the induction phase of the protocol. DepoCyte should never be administered more frequently than every 14th day. Subjects will continue to receive an additional 6 doses of DepoCyte one dose every 28 days (+2 days) during the maintenance period. The first dose will be given 28 days after the last dose in the induction phase.
Drug: Whole Brain Radio Therapy (WBRT) with sequential Depocyte

  Eligibility

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

Indication and Criteria for Inclusion/Exclusion:

Subjects who are to be included in the study have to meet all of the following criteria:

  • Informed consent
  • Male and female, age over 18 years
  • Solid tumour neoplastic meningitis as demonstrated by a positive lumbar CSF cytology (obtained within 21 days prior to treatment initiation) OR Characteristic signs and symptoms of neoplastic meningitis PLUS an MRI indicating the presence of meningeal tumour (diagnosis to be made by neuro-oncologist and confirmed / signed within the CRF). All MRIs will be forwarded for central review and confirmation of diagnosis. In case of discrepancy the central review overrides the assessment of the investigator.
  • CSF flow abnormality excluded by either an MRI scan or a 99Tc-DTPA or 111In-DTPA flow study.

(If a flow abnormality is initially demonstrated but the flow block is subsequently documented by another flow study or MRI scan to be relieved following limited field radiation therapy, the subject may then be eligible)

  • If brain metastasis confirmed (including subjects who have had previous stereotactical radiosurgery or solitary lesion brain surgery) the lesion should be less than 3cm diameter
  • Mini Mental State Examination (MMSE) score more than 24
  • ECOG performance status 0-2

Laboratory values as follows:

  • Platelet count more than or equal to 80,000/mm3
  • ANC more than or equal to 1,000/mm3
  • Serum creatinine less than or equal to 2 x upper limit of normal
  • Total bilirubin less than or equal to 3 x upper limit of normal
  • SGOT (AST) less than or equal to 3 x upper limit of normal
  • LDH less than or equal to 3 x upper limit of normal

    • Females of child-bearing potential must have a negative (urine or serum) pregnancy test within 21 days prior to the start of study treatment.
    • Females of childbearing potential must be willing to use an effective method of contraception to prevent pregnancy for the duration of the study (e.g. implants, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomised partner).
    • Males must be willing to use an effective method of contraception with their partner to prevent pregnancy for the duration of the study (e.g. implants, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomy).

Exclusion Criteria:

  • Previous WBRT
  • Brain metastases more than 3 cm diameter
  • Previous IT treatment
  • Uncontrolled infection including HIV infection
  • Any present condition that is regarded as contraindication for WBRT and intrathecal chemotherapy
  • Prior treatment with systemic ARA-C
  • Anticipated hypersensitivity to DepoCyte or ARA-C
  • Clinically manifest encephalopathy
  • On anticoagulant therapy
  • Ventricular peritoneal CSF drain in situ
  • Subjects unable to comply with study procedures
  • Pregnancy and lactation Any other investigational drug administered within 21 days prior to study entry
  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: NCT00854867

Locations
Austria
Feldkirch Regional Hospital
Feldkirch, Austria
Graz Medical University
Graz, Austria
Univeristy Clinic for Radiotherapy and Radio-Oncology
Innsbruck, Austria
Klagenfurt Regional Hospital
Klagenfurt, Austria
University Internal Medicine Clinic III
Salzburg, Austria
Kaiser-Franz-Josef-Spital
Vienna, Austria
Germany
Heidelbert, Germany
Sponsors and Collaborators
Mundipharma Research Limited
  More Information

Additional Information:
No publications provided

Responsible Party: Mundipharma Research Limited
ClinicalTrials.gov Identifier: NCT00854867     History of Changes
Other Study ID Numbers: DEP1501, 2008-007206-10
Study First Received: March 2, 2009
Last Updated: February 21, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Mundipharma Research Limited:
Solid tumour neoplastic meningitis
STNM
leptomeningeal metastases
DepoCyte
WBRT
Whole Brain Radiotherapy
Liposomal cytarabine intrathecal
Solid Tumour Neoplastic Meningitis with or without brain metastasis

Additional relevant MeSH terms:
Meningitis
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Meningeal Carcinomatosis
Neoplasms
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Meningeal Neoplasms
Cytarabine
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

ClinicalTrials.gov processed this record on July 20, 2014