A Phase I/II Study of ODX (Osteodex) in Metastatic Castration Resistant Prostate Cancer (CRPC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by DexTech Medical AB
Sponsor:
Information provided by (Responsible Party):
DexTech Medical AB
ClinicalTrials.gov Identifier:
NCT01595087
First received: May 8, 2012
Last updated: March 11, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Prostate Cancer Metastatic
Drug: Osteodex
Phase 1
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by DexTech Medical AB:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 28
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)
Arms Assigned Interventions
Experimental: Osteodex, infusion
Osteodex
Drug: Osteodex
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years at the time of signing the informed consent form.
  • Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
  • Failing or not tolerating docetaxel therapy or for other reasons not suitable for such therapy.
  • Evidence of metastatic disease from bone scan (bone lesions) or other imaging modality.
  • Evidence of PSA progression in two consecutive determinations at minimum 1 week interval
  • Castrate levels of serum testosterone ≤1.7 nmol/L.
  • Performance status ECOG 0-2
  • Laboratory requirements:
  • Haematology:
  • Neutrophils ≥ 1.5 x 109/l
  • Haemoglobin ≥ 90 g/l
  • Platelets ≥ 100 x 109/l

Hepatic function:

  • Total S-bilirubin ≤ 1.5 times the upper limit of normal (ULN)
  • AST (SGOT) / ALT (SGPT) ≤ 2.5 times ULN

Renal function:

  • S-Cr ≤ 1.5 times the upper limit of normal (ULN)

Electrolytes:

  • S-sodium, S-potassium, S-calcium (S-albumin corrected), S-phosphate, S-magnesium, all within normal ranges.
  • No evidence (≤5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)
  • Able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  • Concurrent use of other anti-cancer agents or treatments, with the following exception: a stable dose of LHRH agonist/antagonist, polyestradiol phosphate, bicalutamide, flutamide or cyproterone is allowed.
  • Any treatment modalities involving chemotherapy, radiation or major surgery within 4 weeks prior to treatment in this study.
  • Simultaneous participation in any other study involving investigational drugs or having participated in a study less than 4 weeks prior to start of study treatment.
  • Any condition, including the presence of laboratory abnormalities, which confounds the ability to interpret data from the study or places the patient at unacceptable risk if he participates in the study.
  • Known brain metastases.
  • Dental surgery (dental extraction), periodontal disease, local trauma including poorly fitting dentures within 6 months prior to the first dose of study drug.
  • Treatment with bisphosphonates within 4 weeks prior to first dose of study medication.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01595087

Locations
Sweden
Oncology clinic, Skånes Universitetssjukhus i Lund Recruiting
Lund, Sweden, 221 85
Contact: René Blom, M.D.    +46 46 17 10 00    rene.blom@skane.se   
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    claes.nyman@sodersjukhuset.se   
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    camilla.thellenberg@vll.se   
Principal Investigator: Camilla Thellenberg-Karlsson, M.D.         
Sponsors and Collaborators
DexTech Medical AB
Investigators
Study Director: Anders R Holmberg, CEO DexTech Medical AB
  More Information

No publications provided

Responsible Party: DexTech Medical AB
ClinicalTrials.gov Identifier: NCT01595087     History of Changes
Other Study ID Numbers: ODX-001
Study First Received: May 8, 2012
Last Updated: March 11, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by DexTech Medical AB:
CRPC

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 20, 2014