A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via CED In GBM Patients

Inclusion Criteria: To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria ≤ 28 days prior to the anticipated surgery date: 1. Malignant glioma (WHO grade III or IV) who have undergone conventional treatment, including surgery (gross total resection or unintentional partial resection with residual tumour) or biopsy (with residual tumour), and/or radiation therapy, and/or chemotherapy, and/or Temozolomide and have progressive and/or multiple recurrent GBM. Preoperative assessment by clinical presentation and CT/MRI appearance of the lesion will identify suitable candidates. 2. Age 18-75 years. 3. Karnofsky \>70 (see APPENDIX C: EXAMPLE OF PERFORMANCE STATUS: KARNOFSKY SCALE). 4. Stable dose of corticosteroids no longer than 4 weeks prior to enrolment. 5. Females of childbearing potential must have a negative serum or urine pregnancy test. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential. 6. Females of childbearing potential and males who have not undergone surgical sterilization must agree to practice a form of effective contraception prior to entry into the study and for 1 month after the end of infusion. Effective contraception: If female, is non-lactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to entry to the study or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice or be willing to continue to practice acceptable birth control from screening and until 1 month after the study medication has been discontinued. Acceptable birth control includes: 1. Combined (oestrogen and progestogen containing) hormonal contraception; 2. Associated with inhibition of ovulation; oral OR intravaginal OR transdermal; 3. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral OR injectable OR implantable; 4. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action; 5. Intrauterine device (IUD); 6. Intrauterine hormone-releasing system (IUS); 7. Bilateral tubal occlusion; 8. Vasectomised partner; 9. Sexual abstinence; 10. Male or female condom with or without spermicide; 11. Cap, diaphragm or sponge with spermicide. Complies with The Heads of Medicines Agencies (HMA) Recommendations Related to Contraception and Pregnancy Testing in Clinical Trials (Sept 2014). The definition of effective contraception will be based on the judgment of the investigator. 7. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: To be eligible for inclusion into this study, each patient must violate none of the following exclusion criteria ≤ 28 days prior to the anticipated surgery date: 1. Patients who had chemotherapy, radiotherapy or other anti-neoplastic therapy (within 4 weeks or 5x half-life whichever is shorter) prior to study treatment or those who have not recovered to Grade ≤1 or returned to baseline from any acute treatment-related toxicities of the previous therapy except for alopecia and Grade 2 neuropathy. 2. Patients who are receiving any other investigational agents. 3. Life expectancy \<3 months 4. Haematological dysfunction defined as: * White blood cell (WBC) count \<3.0 x 109/L; * Absolute neutrophil count \<1.5 x 109/L; * Haemoglobin level \<10.0 g/dL; * Platelet count \<100 x 109/L. 5. Liver dysfunction defined as: * Aspartate transaminase (AST) \>2.5 x the upper limit of normal (ULN) for age and gender; * Alanine transaminase (ALT) \>2.5 x the ULN for age and gender; * Bilirubin \>1.5 x the ULN for age and gender. 6. Renal dysfunction defined as: \- Creatinine clearance \<60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal for age and gender. 7. Serology indicating active infection with Hepatitis B or C, or HIV. 8. Significant co-morbidity, including coagulation disorders. 9. Pregnancy or unwillingness to practice reliable birth control. 10. Presence of another active malignancy less than 2 years previously (exception: non-melanoma skin cancer). 11. Multifocal, bilateral 12. Midline shift more than 5 mm