A double-blind, multi-centre phase II dose finding study of ODX (Osteodex) in for patients with castration resistant prostate cancer and skeletal metastates

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2015-005666-37-FI
• Date of registration: 26/07/2016
• Prospective Registration: Yes
• Primary sponsor: DexTech Medical AB
• Public title: A double-blind, multi-centre phase II dose finding study of ODX (Osteodex) in for patients with castration resistant prostate cancer and skeletal metastates
• Scientific title: A randomized, 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
• Date of first enrolment: 13/09/2016
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005666-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Study is a dose-finding study divided into three arms with 3, 6 and 9 mg/kg ODX. If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Three different doses of ODX (3, 6 and 9 mg/kg) Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Estonia, Finland, Latvia, Sweden

Contacts

• Name: Public Relations Director
• Affiliation: DexTech Medical AB

• Name: Public Relations Director
• Affiliation: DexTech Medical AB

Key inclusion & exclusion 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
9. Life expectancy =6 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Concurrent use of other anti-cancer agents or treatments, with the following exception: a stable dose of 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



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic Castration Resistant Prostate Cancer (CRPC) and skeletal metastases
MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Osteodex
Product Code: ODX
Pharmaceutical Form: Concentrate and solvent for solution for injection/infusion
INN or Proposed INN: Osteodex
Current Sponsor code: ODX
Other descriptive name: dextran-guanidine-bisphosphonate conjugate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 20-30

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are to compare the effects of three different doses of ODX plus best standard of care on the following:
• progression free survival
• overall survival
• change in response markers related to bone metabolism (B-ALP and S-P1NP) at each timepoint except 12 weeks.
• change in response markers related to bone metabolism (S-CTX and osteocalcin) at each timepoint sampled.
• change in PSA
• time to PSA, B-ALP and S-P1NP progression
• pain (FACT-P and EQ-5D-5L questionnaire)
• analgesic consumption
• therapy response based on changes in tumor cell metabolism according to RECIST measured with CT.
• changes from baseline in bone metastasis by means of bone scan at each time point examined.
• occurrence of symptomatic skeletal events (SSEs; clinically significant pathological fracture, radiation therapy to bone, surgery to bone, or spinal cord compression)
• safety, tolerability and quality of life (FACT-P and EQ-5D-5L questionnaire)

Primary end point(s): Relative change from baseline in response markers related to bone metabolism (B-ALP and S-P1NP) at 12 weeks of three different doses of ODX (3.0, 6.0, 9.0 mg/kg ODX).

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

Timepoint(s) of evaluation of this end point: A DMC (Data Monitoring Committee) will be established to review unblinded study information during the conduct of the study. Based on its review the DMC will provide the sponsor with recommendations regarding study modification, continuation or termination.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The study starts with parallel double-blind randomization of 3 mg/kg and 6 mg/kg. After a minimum number of 12 patients have been randomized to each of the two doses, an unblinded Data Monitoring Committee (DMC) will assess whether or not the study can proceed with enrolment of further patients. The DMC will also assess whether or not the dose level of 9 mg/kg can be included into the randomization. If there should be any concerns, the DMC may recommend a third dose level lower than 9 mg/kg or even lower than 6 mg/kg, i.e., an intermediate dose between 3 and 6 mg/kg.

Secondary end point(s): • Progression free survival, defined as time from randomization until disease progression or death from any cause
• Overall survival, defined as the time from randomization to the date of death from any cause
• Change from baseline in response markers related to bone metabolism (B-ALP and S-P1NP) at each time point sampled (except 12 weeks)
• Change from baseline in response markers related to bone metabolism (S-CTX and osteocalcin) at each time point sampled
• Change from baseline in PSA at each time point sampled
• Time to PSA progression (defined as =25% increase from baseline and an absolute value increase =2 ng/mL at =12 weeks [in patients with no PSA decline from baseline] or =25% increase and an absolute value increase =2 ng/mL above nadir which is confirmed by a second value 3 or more weeks later [in patients with an initial PSA decline from baseline])
• Time to B-ALP progression (defined as =25% increase from baseline at =12 weeks from baseline [in patients with no total B-ALP decline from baseline] or =25% increase above the nadir value which is confirmed by a second value 3 or more weeks later [in patients with an initial total B-ALP decline from baseline])
• Time to S-P1NP progression (defined as =25% increase from baseline at =12 weeks from baseline [in patients with no total S-P1NP decline from baseline] or =25% increase above the nadir value which is confirmed by a second value 3 or more weeks later [in patients with an initial total S-P1NP decline from baseline])
• Time to progression in bone
• Time to progression in soft tissue
• Pain (FACT-P and EQ-5D-5L questionnaire)
• Analgesic consumption
• Therapy response based on changes from baseline according to RECIST criteria based on diagnostic CT in patients with measurable soft tissue metastases
• Change from baseline in bone metastasis by means of bone scan (progression in bone will be defined as at least two or more new lesions on bone scan compared with prior scan at trial entry with a confirmatory bone scan performed 6 or more weeks later showing = 2 additional new lesions (27); therapy response will be assessed based on the difference in BSI from baseline and a threshold of 0.3 BSI-units (28)).
• Occurence of symptomatic skeletal events (SSEs; symptomatic pathological fracture, palliative radiation therapy to bone, surgery to bone, or spinal cord compression)
• Safety, tolerability and quality of life (FACT-P and EQ-5D-5L questionnaire)

Secondary ID(s)

2015-005666-37-SE

ODX-003

Source(s) of Monetary Support

DexTech Medical AB

Ethics review

Status: Approved
Approval date: 16/08/2016
Contact: