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.

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Whole Brain Radio Therapy (WBRT) with sequential Depocyte

Whole brain radiotherapy (WBRT) with concomitant Depocyte

About this trial

This is an interventional treatment trial for Solid Tumour Neoplastic Meningitis focused on measuring Solid tumour neoplastic meningitis, STNM, leptomeningeal metastases, DepoCyte, WBRT, Whole Brain Radiotherapy, Liposomal cytarabine intrathecal, Solid Tumour Neoplastic Meningitis with or without brain metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Feldkirch Regional Hospital
Graz Medical University
Univeristy Clinic for Radiotherapy and Radio-Oncology
Klagenfurt Regional Hospital
University Internal Medicine Clinic III
Kaiser-Franz-Josef-Spital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Whole brain radiotherapy (WBRT) with concomitant Depocyte

Whole Brain Radio Therapy (WBRT) with sequential Depocyte

Arm Description

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.

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.

Outcomes

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.

Secondary Outcome Measures

Overall response rate (ORR)

Progression free survival (PFS)

Time to neurologial progression (TNP)

Overall survival (OS)

Full Information

NCT ID

NCT00854867

First Posted

March 2, 2009

Last Updated

February 21, 2014

Sponsor

Mundipharma Research Limited

1. Study Identification

Unique Protocol Identification Number

NCT00854867

Brief Title

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.

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.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mundipharma Research Limited

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumour Neoplastic Meningitis, Brain Metastases

Keywords

Solid tumour neoplastic meningitis, STNM, leptomeningeal metastases, DepoCyte, WBRT, Whole Brain Radiotherapy, Liposomal cytarabine intrathecal, Solid Tumour Neoplastic Meningitis with or without brain metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Whole brain radiotherapy (WBRT) with concomitant Depocyte

Arm Type

Experimental

Arm Description

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.

Arm Title

Whole Brain Radio Therapy (WBRT) with sequential Depocyte

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Whole Brain Radio Therapy (WBRT) with sequential Depocyte

Intervention Type

Drug

Intervention Name(s)

Whole brain radiotherapy (WBRT) with concomitant Depocyte

Primary Outcome Measure Information:

Title

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