Comparison of TransMID vs Standard Treatment of Cancerous Brain Tumors

Summary: This study will compare the experimental drug TransMID to the best standard treatment for patients with a cancerous brain tumor called glioblastoma multiforme. TransMID is a new type of anti-cancer drug that is being developed to treat recurrent or progressive brain cancers. It contains a protein that attaches to receptors on tumor cells and a toxic substance that affects only tumor cells. Previous studies suggest that TransMID might helpful for patients whose brain tumors do not respond to standard treatments, which may include surgery, radiation, or chemotherapy, or a combination of these modalities.

Patients 18 years of age and older with glioblastoma multiforme whose disease has recurred or progressed after standard treatment may be eligible for this 27-month international study. Participants are randomly assigned to receive either TransMID or the best standard chemotherapy regime offered at the hospital where the patient is receiving care. They undergo the following tests and procedures:

- Chest x-ray if one has not been done in the previous 12 months.

- Electrocardiogram if one has not been done in the previous 6 months.

- Brain biopsy, if results from a recent biopsy (within 90 days) are not available. The biopsy is done in the operating room under general or local anesthesia. A special frame is attached to the skull to allow identification of the correct location for the biopsy. CT or MRI scans are done to help guide the biopsy. A small opening is then made in the skull and a needle is guided into the tumor. A small piece of tumor is withdrawn through the needle for laboratory examination. Patients who are to receive standard chemotherapy then leave the operating room. Patients who are to receive TransMID remain in the operating room for placement of two catheters (thin plastic tubes) into the tumor, guided by CT and MRI scans. After placement, a second CT and MRI are done to check that the catheters are in the correct place. TransMID patients remain in the hospital overnight for monitoring.

- Drug treatment. Patients assigned to chemotherapy receive treatment either as an inpatient or outpatient. Outpatients return to the hospital after 7 days for a neurological examination and blood and urine tests. Patients assigned to TransMID have the drug slowly pumped into the tumor through the catheters for 4 to 7 days, after which the catheters are removed. Patients whose condition remains stable may then leave the hospital. The TransMID treatment is repeated 4 to 8 weeks later.

- Follow-up visits. Patients return to the hospital 10 and 12 and again 16 to 18 days after chemotherapy and after each TransMID treatment for physical and neurological examinations and blood and urine tests. They then return once a month for 6 months for physical and neurological examinations. On some visits, they have an MRI scan and fill out quality of life questionnaires. After 6 months, the number of visits scheduled depends on how well the patient is doing, but all patients return at 9 and 12 months, and then every 3 months for an MRI scan and brief neurological examination as long as the tumor remains stable.

Condition	Treatment or Intervention	Phase
Glioblastoma	Drug: TransMID	Phase III

Study Objectives:

Primary Objective:

To evaluate the efficacy of intratumoral/interstitial therapy with TransMID compared to best standard of care in patients with progressive and/or recurrent, non-resectable glioblastoma multiforme.

Secondary Objectives:

To assess the safety of intratumoral/interstitial therapy with TransMID compared to best standard of care in patients with progressive and/or recurrent, non-resectable glioblastoma multiforme.

To evaluate possible differences in efficacy and/or safety with TransMID associated with differing degrees of transferrin receptor expression in tumor tissue and serum anti-diphtheria toxin antibody titer levels.

Study Design:

Multicenter, open label, randomized study comparing TransMID with a chemotherapeutic regimen considered to be best standard of care and consisting of either nitrosureas, platinum compounds, temozolomide, procarbazine or PCV (procarbazine, lomustine (CCNU) & vincristine). A planned interim analysis of the primary efficacy endpoint will be conducted after approximately 50 percent of the required events have been observed.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Patients will be included in the study if they meet all of the following criteria:
1. Male or female at least 18 years of age.
2. Histological results confirming GBM are available.
3. Progressive GBM (greater than or equal to 25 percent increase in contrast enhanced tumor CSA compared to the nadir or smallest previous measured CSA) and/or recurrent GBM after conventional treatment, including surgery (biopsy or debulking surgery) and/or radiation therapy and/or chemotherapy.
4. Pre-study MRIs used to determine current progression and/or recurrence of GBM are available to the Investigator and for independent confirmation of progression and/or recurrence.
5. Patient is not considered a candidate for resection.
6. If female of child-bearing potential, a reliable method of contraception must be combined with a negative pregnancy test before entering the study (female patients must be willing to use contraception for 2 months after the last treatment with TransMID). Male patients must be willing to use a barrier method of contraception for up to 2 months after the last treatment with TransMID.
7. Able and willing to follow instructions and comply with the protocol.
8. Provide written informed consent prior to participation in the study.
9. Karnofsky Performance Scale Score 70-100.
10. Tumor characteristics:
i) must be unifocal; and
ii) must be unilateral and supratentorial; and
iii) lesion must have a diameter (on contrast-enhanced MRI) greater than or equal to 1.0 cm and less than or equal to 4.0 cm.
EXCLUSION CRITERIA:
Patients will be excluded from the study if they meet any of the following criteria:
1. Anticipated life expectancy of less than 3 months.
2. Infratentorial or intraventricular tumors.
3. Presence of satellite tumors.
4. Chemotherapy within 30 days prior to study entry or nitrosureas or Mitomycin-C containing therapy within 42 days prior to study entry.
5. Radiotherapy or stereotactic (gamma knife) radiosurgery within 90 days prior to study entry.
6. Tumor surgery, tumor debulking or other neurosurgery within 30 days prior to study entry.
7. Previous administration of TransMID.
8. Previous enrolment in this study.
9. Regional therapy including administration of biodegradable polymer wafers containing carmustine within 90 days prior to study entry or brachytherapy within 12 calendar months prior to study entry.
10. Significant liver function impairment (total bilirubin greater than 2.0 mg/dL or 34.2 micromol/L; AST or ALT greater than 3 times the upper limit of normal).
11. Significant renal impairment (serum creatinine greater than 1.7 mg/dL or 150 micromol/L).
12. Coagulopathy (prothrombin time [PT] or activated partial thromboplastin time [APTT] greater than 1.5 times control).
13. Thrombocytopenia (platelet count less than 100 x 10(3)/microL or 100 x 10(9)/L).
14. Granulocytopenia (absolute neutrophil count (ANC), less than 1 x 10(3)/microL or 1.0 x 10(9)/L).
15. Severe acute infection.
16. Medical condition that is considered an unacceptable anesthetic risk.
17. Evidence of a mass effect on CT or MRI with more than a 5 mm midline shift and/or nausea, vomiting, reduced level of consciousness or clinically significant papilledema.
18. Nursing or pregnant females. A pregnancy test will be performed on all females who are of child-bearing potential.
19. Use of any investigational product and/or participation in another clinical research study within the last 30 days prior to study entry.

Maryland
      National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  040244; 04-N-0244
Record last reviewed:  June 28, 2004
Last Updated:  June 28, 2004
Record first received:  July 23, 2004
ClinicalTrials.gov Identifier:  NCT00088400
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08