Study of ODX (Osteodex) in Metastatic Castration Resistant Prostate Cancer (CRPC) (CRPC)

• ClinicalTrials.gov Identifier: NCT02825628
• Recruitment Status: Active, not recruiting
• First Posted: July 7, 2016
• Last Update Posted: February 15, 2019
• Sponsor: DexTech Medical AB
• Information provided by (Responsible Party): DexTech Medical AB

Study Description

Brief Summary:

This is a phase II randomised, double-blind, dose finding, repeat dose Phase II multicentre study of ODX for the treatment of patients with castration resistant prostate cancer (CRPC) and skeletal metastases.

The primary objective is to evaluate the relative change from baseline in response markers related to bone metabolism (alkaline phosphatase (B-ALP) and S P1NP) at 12 weeks of three different doses of ODX (3.0, 6.0 and 9.0 mg/kg ODX).

Condition or disease	Intervention/treatment	Phase
Prostate Cancer Metastatic	Drug: Osteodex	Phase 2

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, height, body temperature and respiratory rate are measured. Blood samples are drawn and urine sample is collected. ECG is recorded. Bone scan and diagnostic CT scan are also 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 recorded, blood samples drawn and urine sample collected. FACT-P and EQ-5D-5L (European Quality of Life - 5 Dimensions with 5 levels) questionnaire are filled out by the subject. Adverse events and concomitant medication is documented and the first dose of the investigational product is given.

The subject is surveyed for 3 hours at the hospital.

The duration of the study for the individual subject will be approximately 20 weeks from screening to the follow-up visit 2 weeks after the last dose. Each subject will receive 10 doses of investigational product. After the follow-up visit, the subject enters to long-term follow-up phase which lasts approximately 2 years.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Dose Finding, Repeat Dose Phase II Multicentre Study of ODX for the Treatment of Patients With Castration Resistant Prostate Cancer (CRPC) and Skeletal Metastases
• Study Start Date: May 2016
• Actual Primary Completion Date: June 2018
• Estimated Study Completion Date: June 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Osteodex 3.0 mg/kg; formulation: solution for infusion route of administration: intravenous infusion	Drug: Osteodex; formulation: solution for infusion route of administration: intravenous infusion; Other Name: ODX
Experimental: Osteodex 6.0 mg/kg; formulation: solution for infusion route of administration: intravenous infusion	Drug: Osteodex; formulation: solution for infusion route of administration: intravenous infusion; Other Name: ODX
Experimental: Osteodex 9.0 mg/kg; formulation: solution for infusion route of administration: intravenous infusion	Drug: Osteodex; formulation: solution for infusion route of administration: intravenous infusion; Other Name: ODX

Outcome Measures

Primary Outcome Measures :

1. Relative change from baseline in response markers related to bone metabolism (B-ALP and S P1NP). [ Time Frame: Baseline and 20 weeks of treatment ]

Secondary Outcome Measures :

1. Progression free survival, defined as the time from study entry to the date of disease progression or death from any cause. [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]
2. Overall survival, defined as the time from randomisation to the date of death from any cause. [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]
3. Change from baseline in response markers related to bone metabolism (B-ALP and S P1NP) at each time point sampled (except 12 weeks). [ Time Frame: Baseline and 20 weeks of treatment ]
4. Change from baseline in response markers related to bone metabolism (Serum C-Terminal Telopeptide (S-CTX) and osteocalcin) at each time point sampled. [ Time Frame: Baseline and 20 weeks of treatment ]
5. Change from baseline in Prostate Specific Antigen (PSA) at each time point sampled. [ Time Frame: Baseline and 20 weeks of treatment ]
6. Time to PSA progression [ Time Frame: Baseline and 20 weeks of treatment ]
7. Time to ALP progression [ Time Frame: Baseline and 20 weeks of treatment ]
8. Time to P1NP progression [ Time Frame: Baseline and 20 weeks of treatment ]
9. Time to progression in bone [ Time Frame: Baseline and 20 weeks of treatment ]
10. Time to progression in soft tissue [ Time Frame: Baseline and 20 weeks of treatment ]
11. Use of analgesics as reported by the patient during treatment and follow-up [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]
12. Therapy response based on changes from baseline according to Response Evaluation Criteria In Solid Tumors (RECIST) based on diagnostic CT in patients with measurable soft tissue metastases. [ Time Frame: Baseline and 20 weeks of treatment ]
13. Changes from baseline in bone metastasis by means of bone scan at each time point examined. [ Time Frame: Baseline and 20 weeks of treatment ]
14. Occurrence of symptomatic skeletal events [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]
15. Pain (FACT-P questionnaire) [ Time Frame: Baseline and 20 weeks of treatment ]
16. Pain (EQ-5D-5L questionnaire) [ Time Frame: Baseline and 20 weeks of treatment ]
17. Quality of life (EQ-5D-5L questionnaire) [ Time Frame: Baseline and 20 weeks of treatment ]
18. Incidence, causality and intensity of Adverse Events (AEs) [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]
19. Dose and duration of medications required for the treatment of AEs [ Time Frame: Baseline, 20 weeks of treatment and long-term follow-up up to 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form
2. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate
3. Evidence of disease progression based on changes in metastatic bone disease (≥2 bone lesions compared to a prior examination) in bone scan and/or other imaging modality AND/OR evidence of PSA progression in the three consecutive determinations at minimum of 1 week intervals
4. Castrate level of serum testosterone ≤1.7 nmol/L
5. Performance status ECOG 0-2

6. 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 or ≤ 5 times ULN in patients with known liver metastases

   Renal function:

   S-creatinine (S-Cr)≤ 1.5 times ULN

7. No evidence (≤ 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)
8. Able to adhere to the study visit schedule and other protocol requirements Life expectancy ≥6 months

Exclusion Criteria:

1. Concurrent use of other anti-cancer agents or treatments, with the following exception: a stable dose of Luteinizing Hormone-Releasing Hormone (LHRH) agonist/antagonist or polyestradiol phosphate. Washout period: bicalutamide 6 weeks; flutamide 4 weeks; abiraterone / enzalutamide 6 weeks, chemotherapy 4 weeks; Radium-223 4 weeks; Strontium-89 or Samarium-153 6 months.
2. Any treatment modalities involving palliative radiation therapy or major surgery within 4 weeks prior to treatment in this study
3. 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
4. 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
5. Known brain metastases
6. Dental surgery (dental extraction), periodontal disease, local trauma including poorly fitting dentures within 6 months prior to the first dose of study drug
7. Treatment with bisphosphonates or denosumab within 4 weeks prior to first dose of study medication

Contacts and Locations

Locations

Estonia

East Tallinn Central Hospital

Tallinn, Estonia, 10138

Tartu University Hospital

Tartu, Estonia, 51014

Finland

Tampere University Hospital, Urology Clinic

Tampere, Finland, 33520

Latvia

Latgales Urology Center

Daugavpils, Latvia, 5401

Pauls Strandins Clinical University Hospital

Riga, Latvia, 1002

Sweden

Urology Clinic, Sodersjukhuset AB

Stockholm, Sweden, 118 83

Oncology Clinic, Norrlands Universitetssjukhus

Umeå, Sweden, 901 85

Örebro University Hospital

Örebro, Sweden, 70185

Sponsors and Collaborators

DexTech Medical AB

Investigators

• Study Director: Anders Holmberg, MD; DexTech Medical AB

More Information

• Responsible Party: DexTech Medical AB
• ClinicalTrials.gov Identifier: NCT02825628
• Other Study ID Numbers: ODX-003
• First Posted: July 7, 2016
• Last Update Posted: February 15, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases