A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via CED In GBM Patients
The purpose of the study is to evaluate the feasibility and safety of intra-tumor and interstitial therapy with hBMP4 in increasing doses in patients with progressive and/or multiple recurrent Glioblastoma multiforme (GBM).
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
|Eligible Ages||18 Years - 75 Years|
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.
- - 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.
- - Creatinine clearance <60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal for age and gender.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 0: Exploratory study involving very limited human exposure to the drug to determine whether a drug is modulating its target.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Countries||Israel, Italy, Netherlands|
The disease, disorder, syndrome, illness, or injury that is being studied.
This multicentre, open-label, dose escalating, Phase I study will enrol approximately 18 patients with progressive and/or multiple recurrent GBM, who after failure of standard therapies will receive GMP Human- recombinant Bone Morphogenetic Protein 4 via intra-tumour and interstitial delivery by CED. Patients will undergo a resection or biopsy of the tumour, confirmation of viable malignant glioma tumour cells during frozen section performed by the institutional pathologists, and intra-tumor and interstitial placement under neuronavigational guidance of 2 or 3 catheters. No catheters will be placed at time of resection. After resection, catheters will be placed during a separate procedure several days later based upon the patient's condition as determined by both a clinical examination and routine MRI scan. Patients will receive intra-tumour and interstitial CED of increasing amounts of hrBMP4 solutions (at a starting dose of 0.5 mg) and 1:70 gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) in a total of 44-66 ml over up to 4-6 days at the discretion of the investigator. Gd-DTPA will be co-infused with hrBMP4 to determine the extent of intra-tumour and interstitial drug delivery. Patients will be hospitalized from the time of the original surgery until the end of infusion of hrBMP4. Patients will be followed for the duration of the study. The primary endpoint of the study is monitoring feasibility and patient safety for the incidence of Dose-Limiting Toxicity (DLT) following intra-tumour and interstitial therapy with hrBMP4 and to determine whether there is a Maximum Tolerated Dose (MTD).
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Not yet recruiting
Tel Aviv Sourasky Medical Center
Tel Aviv, ,
Not yet recruiting
Istituto Neurologico Carlo Besta
Milano, , 20133
Erasmus University Medical Center, Department of Neurosurgery
Rotterdam, , 3000