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MDPK67b in Patients With Prostate Cancer

Sponsor
Med Discovery SA (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05580107
Collaborator
Camara and Partners Sàrl (Other), Soladis (Other)
15
Enrollment
1
Location
1
Arm
24.7
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Administration of MDPK67b to assess its Tolerability and Safety profile in prostate cancer patients, and to assess histo-pathological and molecular changes in prostate tumor tissue samples.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Dose finding (24 and 48 mg) based on dose limiting toxicity (DLT)Dose finding (24 and 48 mg) based on dose limiting toxicity (DLT)
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-label Phase Ib Study of Preoperative Treatment With the KLK Inhibitor MDPK67b in Patients With Untreated Prostate Cancer
Actual Study Start Date :
Aug 9, 2021
Anticipated Primary Completion Date :
Aug 31, 2023
Anticipated Study Completion Date :
Aug 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose

Five patients will be included into the 24 mg dose level. In case of dose limiting toxicity (DLT) in at least one patient, 5 additional patients will be enrolled in the 24 mg dose level. If the treatment is well tolerated, i.e. no DLT is encountered, the dose of MDPK67b is escalated to 48 mg on a second cohort of 5 patients. In case of DLT in at least one patient at the 48 mg dose level, the 24 mg dose level of MDPK67b is expanded from 5 to 10 patients, or declared the maximum tolerated dose (MTD) if already expanded to 10 patients.

Drug: MDPK67b
24 mg or 48 mg

Outcome Measures

Primary Outcome Measures

  1. Tolerability and Safety [Day 1]

    Number of subjects with changes in blood pressure

  2. Tolerability and Safety [Day 8]

    Number of subjects with changes in blood pressure

  3. Tolerability and Safety [Day 15]

    Number of subjects with changes in blood pressure

  4. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in blood pressure

  5. Tolerability and Safety [Day 1]

    Body temperature

  6. Tolerability and Safety [Day 8]

    Number of subjects with changes in body temperature

  7. Tolerability and Safety [Day 15]

    Number of subjects with changes in body temperature

  8. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in body temperature

  9. Tolerability and Safety [Day 1]

    Number of subjects with changes in respiration rate

  10. Tolerability and Safety [Day 8]

    Number of subjects with changes in respiration rate

  11. Tolerability and Safety [Day 15]

    Number of subjects with changes in respiration rate

  12. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in respiration rate

  13. Tolerability and Safety [Day 1]

    Number of subjects with changes in weight

  14. Tolerability and Safety [Day 8]

    Number of subjects with changes in weight

  15. Tolerability and Safety [Day 15]

    Number of subjects with changes in weight

  16. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in weight

  17. Tolerability and Safety [Day 1]

    Number of subjects with changes in QTc on ECG

  18. Tolerability and Safety [Day 8]

    Number of subjects with changes in QTc on ECG

  19. Tolerability and Safety [Day 15]

    Number of subjects with changes in QTc on ECG

  20. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in QTc on ECG

  21. Tolerability and Safety [Day 1]

    Number of subjects with changes in heart rate on ECG

  22. Tolerability and Safety [Day 8]

    Number of subjects with changes in heart rate on ECG

  23. Tolerability and Safety [Day 15]

    Number of subjects with changes in heart rate on ECG

  24. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in heart rate on ECG

  25. Tolerability and Safety [Day 8]

    Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen

  26. Tolerability and Safety [Day 15]

    Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen

  27. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen

  28. Tolerability and Safety [Day 8]

    Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA

  29. Tolerability and Safety [Day 15]

    Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA

  30. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA

  31. Tolerability and Safety [Day 8]

    Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin

  32. Tolerability and Safety [Day 15]

    Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin

  33. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin

  34. Tolerability and Safety [Day 1]

    Number of subjects with changes in physical examination

  35. Tolerability and Safety [Day 8]

    Number of subjects with changes in physical examination

  36. Tolerability and Safety [Day 15]

    Number of subjects with changes in physical examination

  37. Tolerability and Safety [Day 20-25]

    Number of subjects with changes in physical examination

  38. Tolerability and Safety [Day 1]

    Adverse events

  39. Tolerability and Safety [Day 8]

    Adverse events

  40. Tolerability and Safety [Day 15]

    Adverse events

  41. Tolerability and Safety [Day 20-25]

    Adverse events

  42. Tolerability and Safety [Day 1]

    Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)

  43. Tolerability and Safety [Day 8]

    Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)

  44. Tolerability and Safety [Day 15]

    Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)

Secondary Outcome Measures

  1. Histo-pathological and molecular changes in prostate tumor tissue samples [Screening (Diagnostic biopsy)]

    Androgen receptor expression

  2. Histo-pathological and molecular changes in prostate tumor tissue samples [Day 16/17 (Radical prostatectomy sample)]

    Androgen receptor expression

  3. Histo-pathological and molecular changes in prostate tumor tissue samples [Screening (Diagnostic biopsy)]

    Extent of proliferation using Ki67

  4. Histo-pathological and molecular changes in prostate tumor tissue samples [Day 16/17 (Radical prostatectomy sample)]

    Extent of proliferation using Ki67

  5. Histo-pathological and molecular changes in prostate tumor tissue samples [Screening (Diagnostic biopsy)]

    Extent of inflammation using leukocyte markers

  6. Histo-pathological and molecular changes in prostate tumor tissue samples [Day 16/17 (Radical prostatectomy sample)]

    Extent of inflammation using leukocyte markers

  7. Histo-pathological and molecular changes in prostate tumor tissue samples [Screening (Diagnostic biopsy)]

    Expression of KLK2, KLK4, and KLK14 using immunohistochemistry

  8. Histo-pathological and molecular changes in prostate tumor tissue samples [Day 16/17 (Radical prostatectomy sample)]

    Expression of KLK2, KLK4, and KLK14 using immunohistochemistry

  9. Histo-pathological and molecular changes in prostate tumor tissue samples [Screening (Diagnostic biopsy)]

    Treatment induced change in RNA transcriptome assessed by RNA sequencing

  10. Histo-pathological and molecular changes in prostate tumor tissue samples [Day 16/17 (Radical prostatectomy sample)]

    Treatment induced change in RNA transcriptome assessed by RNA sequencing

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No

Subject screening criteria

  1. Patients aged 18 years or older.

  2. Patients who have untreated suspected PCa or PCa under active surveillance (AS) with progression/upgrading.

  3. Patients who signed a written screening phase ICF.

Subject non-screening criteria

  1. Patients who have an uncontrolled disease that would unduly increase the risk of toxicity or limit compliance with study requirements in the opinion of the Investigator; including but not limited to: ongoing or active symptomatic infection, uncontrolled diabetes mellitus, diseases of the coagulation system, unstable or uncompensated cardiac, hepatic, renal, respiratory, or psychiatric disease.

  2. Patients who required a significant change in their concomitant medications during the week prior to screening visit, or who will likely need to have a change in their concomitant medications during the study. This includes any medication other than those required for PCa diagnosis or for RPE.

  3. Patients who have received prior radiotherapy to the prostate.

  4. Patients who have had prior exposure to MDPK67b.

  5. Patients who have participated in another clinical trial within 3 months prior to screening visit, except if in the opinion of the investigator the type of trial does not interfere in any way with the present trial (eg. non-interventional observational trial). In case of doubt, the sponsor's prior approval must be obtained and the decision to include such a patient will be documented in detail.

Non-screening criteria are exclusion criteria for the screening phase.

For the patients not participating in the screening phase (ie patients with previously established PCa diagnosis), all the criteria above shall be checked prior to enrolment in the treatment phase. However, these patients do not have to sign a screening ICF (screening criterion n°3 is not applicable), and for non-screening criterion n°5, the 3-month wash-out period is prior to the inclusion visit in the treatment phase.

Subject inclusion criteria

  1. Patients who still meet all the eligibility criteria checked at screening visit.

  2. Patients who have untreated PCa with a Gleason score of 7 (preferably) or higher, with local disease or with metastatic disease (if metastatic, no visceral metastases, no more than five bone or lymph node metastases), and are scheduled to undergo RPE about 3 weeks later.

  3. Patients with an expected minimal survival time of 12 months.

  4. Patients who have an acceptable organ and marrow function as assessed at the inclusion visit and defined as follows:

  5. Absolute neutrophil count ≥ 1.5 × 109/L.

  6. Platelets ≥ 100 × 109/L.

  7. Hemoglobin ≥ 9 g/dL.

  8. Total bilirubin ≤ 1.5 × ULN, unless the patient has known Gilbert's syndrome.

  9. Aspartate amino transferase (AST) and alanine amino transferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN in presence of liver metastasis.

  10. Serum creatinine ≤ 2.0 × ULN, or GFR ≥ 30 mL/min by Cockcroft-Gault.

  11. INR <1.5, aPTT < 60 s

  12. Patients with an ECOG performance status ≤ 1.

  13. Patients who agree to refrain to donate sperm for the duration of the study.

  14. Patients who signed a written treatment phase ICF.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Klinik für Urologie, UniversitätSpital Zürich (USZ) Zürich Switzerland 8091

Sponsors and Collaborators

  • Med Discovery SA
  • Camara and Partners Sàrl
  • Soladis

Investigators

  • Principal Investigator: Daniel Eberli, Prof., Klinik für Urologie, UniversitätSpital Zürich (USZ)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Med Discovery SA
ClinicalTrials.gov Identifier:
NCT05580107
Other Study ID Numbers:
  • MDPK67b-2002
First Posted:
Oct 14, 2022
Last Update Posted:
Oct 14, 2022
Last Verified:
Oct 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Med Discovery SA
prostate cancer
radical prostatectomy
Gleason score 7 or higher
Additional relevant MeSH terms:
Prostatic Neoplasms

Study Results

No Results Posted as of Oct 14, 2022