Psma Intensity Can be Altered by Androgen and Phospho-SrC Obstruction (PICASSO)
Primary Purpose
Metastatic Prostate Cancer
Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Dasatinib
Darolutamide
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Male, aged 18 years or older
- Pathologically confirmed adenocarcinoma of prostate or a clinical presentation consistent with prostate cancer
- Metastatic castrate resistant prostate cancer previously confirmed on 68Ga-PSMA-11 and 18F-FDG imaging to be inadequate for future PSMA-directed theranostic treatment by a nuclear medicine physician based on FDG-discordance (FDG-positive, PSMA-negative sites of disease) OR low PSMA SUV values within 2 weeks of starting study drug
- Adequate hematologic and organ function within 14 days before the first study treatment
- Castrate levels of testosterone < 1.7 ng/ml
- Provision of written informed consent.
Exclusion Criteria:
- Patients who cannot lie still for at least 30 minutes or comply with imaging.
- Previous dasatinib for prostate cancer or other condition, eg CLL
- Allergy to dasatinib or darolutamide
- Use of drugs that interact with interact pharmacologically with dasatinib within 1 week of study entry eg Use of CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St John's Wort) and use of CYP3A4 substrates with narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot analogues.
- Use Concomitant use of H2 antagonists or proton pump inhibitors.
- Current or previous (within the last 6 months) pleural effusion
- Use of paracetamol during the study period
- Subjects may not have any of the following: Clinical evidence of uncontrolled heart failure, myocardial infarction, or angina within the previous 6 months; prolonged QT interval Fridericia's (QTcF) > 450msec; history of unstable ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, or torsades de pointes); concomitant use of drugs known to cause torsades de pointes [quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,pentamidine, sparfloxacin, lidoflazine] (these agents must have been discontinued at least 7 days prior to starting dasatinib)
- Subjects may not be enrolled with any of the following: History of a significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any cause within 3 months
Sites / Locations
- Kinghorn Cancer Centre, St. Vincent's HospitalRecruiting
- Peter MacCallum Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Cohort A
Cohort B
Arm Description
Dasatinib 100mg once daily orally for 14 Days
Dasatinib 100mg once daily and Darolumatide 600 mg twice daily orally for 14 Days
Outcomes
Primary Outcome Measures
To quantify the increase in tumour (standard uptake value) SUV measurements comparing baseline to 2-week PSMA PET scans in men being treated with dasatinib alone or in combination with darolutamide
Primary outcome
Secondary Outcome Measures
To determine the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after a 14-day course of dasatinib alone or in combination with darolutamide in men with castrate resistant prostate cancer
Secondary outcome
Full Information
NCT ID
NCT04925648
First Posted
March 23, 2021
Last Updated
April 10, 2023
Sponsor
St Vincent's Hospital, Sydney
1. Study Identification
Unique Protocol Identification Number
NCT04925648
Brief Title
Psma Intensity Can be Altered by Androgen and Phospho-SrC Obstruction
Acronym
PICASSO
Official Title
PICAASO / CA180-722: Psma Intensity Can be Altered by Androgen and Phospho-SrC Obstruction
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2021 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St Vincent's Hospital, Sydney
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study's purpose is to understand the appearance of your prostate-specific membrane antigen (PSMA) PET scan after you take 14 days of treatment with a drug called dasatinib alone or in combination with anti-testosterone drug call darolutamide.
Who is it for? You may be eligible to join this study if you have metastatic prostate cancer and had a recent PSMA scan showing low PSMA uptake
Study Details:
Participants will receive dasatinib 100 mg daily or dasatinib 100 mg daily and darolutamide 600 mg twice daily for 14 days. They will undergo another PSMA PET scan after 14 days. Participants will be followed up on day 7 of treatment and 30 days after treatment.
It is hoped that this research will provide insight into the mechanism of PSMA expression in advanced prostate cancer.
Detailed Description
Our group has previously established a strong interaction between the androgen receptor and PSMA receptor in both castrate sensitive and castrate resistant prostate cancers that impacts on the density of PSMA expression. Recent lab studies have also revealed that phospho-SRC inhibition with drugs such as dasatinib can also modulate PSMA expression, in particular in combination with androgen signalling inhibition. If so, this can influence both the timing and use of PSMA PET scans, PSMA based radionuclide therapies and PSMA immunotherapies. In this study we plan to validate and quantify the change in PSMA PET scan SUV when patients undergo a 14 days treatment with dasatinib alone or in combination with an androgen signalling inhibitor (darolutamide).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Prospective, non-randomised pilot study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort A
Arm Type
Active Comparator
Arm Description
Dasatinib 100mg once daily orally for 14 Days
Arm Title
Cohort B
Arm Type
Active Comparator
Arm Description
Dasatinib 100mg once daily and Darolumatide 600 mg twice daily orally for 14 Days
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Intervention Description
Dasatinib 100mg once daily orally for 14 Days
Intervention Type
Drug
Intervention Name(s)
Darolutamide
Intervention Description
Darolumatide 600 mg twice daily orally for 14 Days
Primary Outcome Measure Information:
Title
To quantify the increase in tumour (standard uptake value) SUV measurements comparing baseline to 2-week PSMA PET scans in men being treated with dasatinib alone or in combination with darolutamide
Description
Primary outcome
Time Frame
14 days
Secondary Outcome Measure Information:
Title
To determine the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after a 14-day course of dasatinib alone or in combination with darolutamide in men with castrate resistant prostate cancer
Description
Secondary outcome
Time Frame
14 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male, aged 18 years or older
Pathologically confirmed adenocarcinoma of prostate or a clinical presentation consistent with prostate cancer
Metastatic castrate resistant prostate cancer previously confirmed on 68Ga-PSMA-11 and 18F-FDG imaging to be inadequate for future PSMA-directed theranostic treatment by a nuclear medicine physician based on FDG-discordance (FDG-positive, PSMA-negative sites of disease) OR low PSMA SUV values within 2 weeks of starting study drug
Adequate hematologic and organ function within 14 days before the first study treatment
Castrate levels of testosterone < 1.7 ng/ml
Provision of written informed consent.
Exclusion Criteria:
Patients who cannot lie still for at least 30 minutes or comply with imaging.
Previous dasatinib for prostate cancer or other condition, eg CLL
Allergy to dasatinib or darolutamide
Use of drugs that interact with interact pharmacologically with dasatinib within 1 week of study entry eg Use of CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St John's Wort) and use of CYP3A4 substrates with narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot analogues.
Use Concomitant use of H2 antagonists or proton pump inhibitors.
Current or previous (within the last 6 months) pleural effusion
Use of paracetamol during the study period
Subjects may not have any of the following: Clinical evidence of uncontrolled heart failure, myocardial infarction, or angina within the previous 6 months; prolonged QT interval Fridericia's (QTcF) > 450msec; history of unstable ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, or torsades de pointes); concomitant use of drugs known to cause torsades de pointes [quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,pentamidine, sparfloxacin, lidoflazine] (these agents must have been discontinued at least 7 days prior to starting dasatinib)
Subjects may not be enrolled with any of the following: History of a significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any cause within 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony Joshua, FRACP, MBBS, PhD
Phone
+61 293555655
Email
Anthony.Joshua@svha.org.au
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Kent
Phone
+61 293555611
Email
SVHS.CancerResearch@svha.org.au
Facility Information:
Facility Name
Kinghorn Cancer Centre, St. Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Kent
Phone
0293555611
Email
SVHS.CancerResearch@svha.org.au
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arun Azad, FRACP, MBBS, PhD
Email
arun.azad@petermac.org
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No Plan to share participant data with individuals outside this trial
Learn more about this trial
Psma Intensity Can be Altered by Androgen and Phospho-SrC Obstruction
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