TransMID treatment or best standard of care for patients with advanced glioblastoma multiforme

Glioblastoma multiforme (GBM) is a type of brain tumour. GBM tumours are usually treated with surgery and radiotherapy. Unfortunately, this type of brain tumour may continue to grow or come back (recur) despite treatment.

This trial will compare a new drug called TransMID with the best standard treatment that is currently available. TransMID is a drug that is a combination of a protein called transferrin and a poison called diphtheria toxin.

Cancer cells need iron in order to continue to grow. They need more iron than normal cells. Transferrin helps cells to take up available iron. So the cancer cells are attached to the transferrin in TransMID, and the diphtheria poison kills them. The aim of this treatment is to kill the cancer cells while not affecting the normal brain cells. This treatment for brain tumours may have fewer side effects than other treatments because it targets cancer cells.

The best standard treatment will involve giving chemotherapy. You may have chemotherapy as part of the treatment when you are diagnosed. Or it may be kept in reserve to treat your brain tumour if it comes back or continues to grow. Your cancer specialist (consultant) will decide which chemotherapy drugs you should have.

Condition	Treatment or Intervention	Phase
Glioblastoma Multiforme	Drug: TransMID™	Phase III

This is a Multicenter, open label, randomized study comparing TransMID™ with a chemotherapeutic regimen considered to be best standard of care and consisting of either nitrosoureas, 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% of the required events have been observed.

In order for a patient to be eligible for enrollment into this trial, he/she must be diagnosed with glioblastoma multiforme which has been confirmed histologically and have undergone conventional treatment, including surgery (biopsy or debulking) and/or radiation therapy and/or chemotherapy, have a recurrent and/or progressive tumor ≥1.0 cm and ≤4.0 cm in diameter.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Male or female at least 18 years of age
• Histological results confirming GBM are available
• Progressive GBM (≥ 25% 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
• 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
• Patient is not considered a candidate for resection
• 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™
• Able and willing to follow instructions and comply with the protocol
• Provide written informed consent prior to participation in the study
• Karnofsky Performance Scale Score 70-100
• Tumor characteristics: i) must be unifocal; and ii) must be unilateral and supratentorial; and iii) lesion must have a diameter (on contrast-enhanced MRI) ≥1.0 cm and ≤4.0 cm

Exclusion Criteria:

• Anticipated life expectancy of less than 3 months
• Infratentorial or intraventricular tumors
• Presence of satellite tumors
• Chemotherapy within 30 days prior to study entry or nitrosoureas or Mitomycin-C containing therapy within 42 days prior to study entry
• Radiotherapy or stereotactic (gamma knife) radiosurgery within 90 days prior to study entry
• Tumor surgery, tumor debulking or other neurosurgery within 30 days prior to study entry
• Previous administration of TransMID™
• Previous enrollment in this study
• 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
• Significant liver function impairment (total bilirubin > 2.0 mg/dL or 34.2 μmol/L; AST or ALT > 3 times the upper limit of normal)
• Significant renal impairment (serum creatinine > 1.7 mg/dL or 150 µmol/L)
• Coagulopathy (prothrombin time [PT] or activated partial thromboplastin time [APTT] >1.5 times control)
• Thrombocytopenia (platelet count < 100 x 103/μL or 100 x 109/L)
• Granulocytopenia (absolute neutrophil count (ANC), < 1 x 103/μL or 1.0 x 109/L)
• Severe acute infection
• Medical condition that is considered an unacceptable anesthetic risk
• 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
• Nursing or pregnant females. A pregnancy test will be performed on all females who are of child-bearing potential
• Use of any investigational product and/or participation in another clinical research study within the last 30 days prior to study entry

Patrick M Rossi, MD      856-273-6057    patrick_rossi@xenova.co.uk
Ronald Monroe, MD      856-273-6057    ron_monroe@xenova.co.uk

California
      University of Southern California, Los Angeles,  California,  United States; Recruiting
Colorado
      University of Colorado Health Sciences Center, Denver,  Colorado,  United States; Recruiting
Florida
      Moffitt Cancer Center and Research Institute, Tampa,  Florida,  United States; Recruiting
      Mayo Clinic, Jacksonville,  Florida,  United States; Recruiting
Illinois
      University of Chicago, Chicago,  Illinois,  United States; Recruiting
Iowa
      University of Iowa Hospitals in Clinics, Cedar Rapids,  Iowa,  United States; Recruiting
Kentucky
      University of Kentucky Medical Center, Lexington,  Kentucky,  United States; Recruiting
Maryland
      NINDS National Institutes of Health, Bethesda,  Maryland,  United States; Recruiting
      Johns Hopkins Medical Center, Baltimore,  Maryland,  United States; Recruiting
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  United States; Recruiting
Missouri
      Saint Louis University Hospital, St. Louis,  Missouri,  United States; Recruiting
New York
      SUNY Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  United States; Recruiting
Pennsylvania
      Temple University Hospital, Philadelphia,  Pennsylvania,  United States; Recruiting
South Carolina
      Medical University of South Carolina, Charlston,  South Carolina,  United States; Recruiting
Utah
      University of Utah, Salt Lake City,  Utah,  United States; Recruiting

Study ID Numbers:  KSB311R/CIII/001
Record last reviewed:  October 2004
Record first received:  May 24, 2004
ClinicalTrials.gov Identifier:  NCT00083447
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-10