A Phase I/II Study of ODX (Osteodex) in Metastatic Castration Resistant Prostate Cancer (CRPC)
This phase I/IIa study is a multi-center, prospective, open-label study evaluating safety and biological efficacy of up to six dose levels of Osteodex of patients with metastatic castration resistant prostate cancer (CRPC). Osteodex is a poly-bisphosphonate containing three known substances; dextran, alendronate and guanidine.
The objective of the study is to define the maximum tolerable dose of Osteodex when given every third week. The following objectives will also be evaluated: overall survival, PSA response, response markers related to bone metabolism (S-ALP and U-NTx), Quality of Life and assessment of pharmacokinetic parameters.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of ODX (Osteodex) in Metastatic Castration Resistant Prostate Cancer (CRPC)|
- To define the maximum tolerable dose (MTD) of Osteodex. [ Time Frame: up to 21 weeks ] [ Designated as safety issue: No ]The MTD will be defined as the dose that is a predecessor to the dose where dose limiting toxicity (DLT, e.g., lack of recovery to baseline of serum creatinine (S-Cr), clinically significant abnormalities in test results for haematology, liver function, electrolytes, calcium, clinically significant ECG changes) occurs within 3 weeks after administration for at least 1 among 4 subjects. In case such dose limiting toxicity (DLT) is not observed for any doses the maximum dose at 1.5 mg/kg will be defined as the MTD.
- Evaluation of overall survival [ Time Frame: Baseline and 21 weeks ] [ Designated as safety issue: No ]
- PSA response [ Time Frame: Baseline and 21 weeks ] [ Designated as safety issue: No ]
- Response markers related to bone metabolism (S-ALP and U-NTx) [ Time Frame: Baseline and 21 weeks ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: Baseline and 21 weeks ] [ Designated as safety issue: No ]FACT-P questionnaire
- Assessment of blood half life [ Time Frame: pre-infusion and 30 min, 1 hr, 2 hrs, 3 hrs and 6 hrs post infusion ] [ Designated as safety issue: No ]
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||September 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Osteodex, infusion
Seven cohorts; Dose cohort 1; 0.1 mg/kg given every third week, maximum 7 times. Dose cohort 2; 0.3 mg/kg given every third week, maximum 7 times. Dose cohort 3; 0.6 mg/kg given every third week, maximum 7 times. Dose cohort 4; 0.9 mg/kg given every third week, maximum 7 times. Dose cohort 5; 1.2 mg/kg given every third week, maximum 7 times. Dose cohort 6; 1.5 mg/kg given every third week, maximum 7 times. Dose cohort 7; 3.0 mg/kg given every third week, maximum 7 times.
Other Name: Castration resistant prostate cancer
Males, diagnosed with CRPC, who fulfil the inclusion criteria and does not have any exclusion criteria, will be asked to participate in the study. The subject will be informed orally and in writing about the study procedures and give written informed consent, prior to study start. At the screening visit the following examinations are performed: Physical examination, medical history and concomitant medication. Heart rate, blood pressure, weight, body temperature and respiratory rate are measured. Blood samples are drawn and urine sample is collected. ECG is performed. At the next visit, baseline, the subject is examined physically and heart rate, blood pressure, weight, body temperature and respiratory rate are measured, ECG is performed, blood samples drawn and urine sample collected. FACT-P questionnaire is filled out by the subject. Adverse events and concomitant medication is documented and the first dose of the investigational product is given. The subject will be consecutively assigned to the dose cohorts, starting with the lowest dose cohort, cohort one out of seven cohorts.
Then the subject is surveyed during 24 hours at the hospital. Prior to discharge from the hospital the same examinations are done as described above.
The duration of the study for the individual subject will be approximately 25 weeks from screening to the follow-up visit 3 weeks after the last dose. Each subject will receive at least 4 doses and maximum 7 doses of investigational product.
A Data Monitoring Committee (DMC) will be designated and will be responsible to monitor/review all study related safety data. After review of safety data the DMC will provide recommendation as to whether the dose escalation can proceed as planned according to the protocol.
|Oncology clinic, Skånes Universitetssjukhus i Lund||Recruiting|
|Lund, Sweden, 221 85|
|Contact: René Blom, M.D. +46 46 17 10 00 email@example.com|
|Principal Investigator: René Blom, M.D.|
|Urology clinic, Södersjukhuset AB||Recruiting|
|Stockholm, Sweden, 118 83|
|Contact: Claes Nyman, M.D. +46 8-616 10 00 firstname.lastname@example.org|
|Principal Investigator: Claes Nyman, M.D.|
|Oncology clinic, Norrlands Universitetssjukhus||Recruiting|
|Umeå, Sweden, 901 85|
|Contact: Camilla Thellenberg-Karlsson, M.D. +46 90 785 0000 email@example.com|
|Principal Investigator: Camilla Thellenberg-Karlsson, M.D.|
|Study Director:||Anders R Holmberg, CEO||DexTech Medical AB|