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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03658447




Registration number
NCT03658447
Ethics application status
Date submitted
23/08/2018
Date registered
5/09/2018

Titles & IDs
Public title
PRINCE (PSMA-lutetium Radionuclide Therapy and ImmuNotherapy in Prostate CancEr)
Scientific title
Phase Ib/II Study of Radionuclide 177Lutetium-PSMA-617 Therapy in Combination With Pembrolizumab for Treatment of Metastatic Castration Resistant Prostate Cancer (mCRPC)
Secondary ID [1] 0 0
PeterMac project no. 18/114
Universal Trial Number (UTN)
Trial acronym
PRINCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration Resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - 177Lu-PSMA

Experimental: 177Lu-PSMA + Pembrolizumab - 200mg pembrolizumab given 3 weekly for upto 35 cycles and 6-weekly 177Lu-PSMA treatments for upto 6 cycles starting at 8.5GBq with administered radioactivity reduced by 0.5GBq for each cycle.


Treatment: Drugs: Pembrolizumab
200mg Pembrolizumab given 3 weekly for upto 35 cycles

Treatment: Drugs: 177Lu-PSMA
6-weekly 177Lu-PSMA treatments for upto 6 cycles starting at 8.5GBq with administered radioactivity reduced by 0.5GBq for each cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate Specific Antigen (PSA) response
Timepoint [1] 0 0
Through study completion, up until 24 months after the last patient commences treatment.
Primary outcome [2] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety]
Timepoint [2] 0 0
Through treatment completion, maximum of 24 months
Primary outcome [3] 0 0
Tolerability
Timepoint [3] 0 0
Through treatment completion, maximum of 24 months
Secondary outcome [1] 0 0
Radiographic progression free survival
Timepoint [1] 0 0
Through study completion, up until 24 months after the last patient commences treatment.
Secondary outcome [2] 0 0
PSA-progression free survival
Timepoint [2] 0 0
Through study completion, up until 24 months after the last patient commences treatment.
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [4] 0 0
Overall Response Rate by modified RECIST1.1
Timepoint [4] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [5] 0 0
Duration of objective tumour response as assessed by modified RECIST 1.1 for soft tissue and PCWG3 for bone lesions
Timepoint [5] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [6] 0 0
Time to treatment (TTR) response
Timepoint [6] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [7] 0 0
Change in pain
Timepoint [7] 0 0
Through treatment completion, maximum of 24 months
Secondary outcome [8] 0 0
Change in Health Related Quality of Life (HRQoL)
Timepoint [8] 0 0
Through treatment completion, maximum of 24 months

Eligibility
Key inclusion criteria
Patients must meet the following criteria for study entry:

1. Patient who are at least 18 years of age who have provided written informed consent.
2. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
3. Eastern Cooperative Oncology Group (ECOG) performance status of = 1 (see Appendix 1).
4. Patients must have progressed on prior enzalutamide, abiraterone and/or apalutamide for treatment of prostate cancer.
5. Determination of disease progression on second generation androgen receptor targeted agent determined by the local investigator. Progressive disease is defined by PCWG3 as any one of the following:

* PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of = 1 week between each measurement. The PSA value at screening should be = 1ng/ml.
* Soft tissue or visceral disease progression as per modified RECIST 1.1 criteria (see Appendix 2)
* Bone progression: = 2 new lesions on bone scan (Appendix 2)
6. At least 2 weeks since the completion of surgery or radiotherapy prior to registration. Any clinically relevant sequelae from the surgery or radiotherapy must have improved to grade 1 prior to registration.
7. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist). Patients without prior surgical castration must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) therapy throughout the duration of study treatment.
8. Serum testosterone levels = 50ng/dL. (= 1.75nmol/L) within 28 days before registration.
9. Imaging evidence of metastatic disease documented with either bone scan or CT scan (Appendix 2).
10. Prior prostate cancer vaccine therapy, radiation therapy, systemic therapies, diethylstilboestrol (DES) or other estrogens are allowed up to 28 days prior to trial registration. Note: bicalutamide flutamide or nilutamide must be discontinued within 4 weeks of registration.
11. Significant PSMA avidity on 68Ga/18F-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at other sites of disease =10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
12. Patients must have a life expectancy = 24 weeks.
13. Patients must agree to use a highly effective form of contraception for the entire duration of the study plus an additional 120 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period (see section 10.3.3).
14. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled assessments.
15. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days of registration, defined as:

* Haemoglobin =90 g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
* White blood cells >3x109/L
* Absolute neutrophil count =1.5x109/L
* Platelets =100 x109/L
* Total bilirubin =1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome.
* Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) =2.5 × ULN or =5 × ULN for participants with liver metastases.
* Serum creatinine =1.5 x ULN or a calculated creatinine clearance > 50mL/min (Chronic Kidney Disease Epidemiology (CKD-EPI) equation for patients with creatinine levels above institutional normal.
* Albumin >30 g/dl
* International normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (aPTT) =1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
16. Patients who are deemed by PSMA imaging to have readily accessible disease will be required to consent to 3 serial tumour biopsies - at screening, post combination treatment (at any time between weeks 2-4) and on progression
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Site(s) of disease that are FDG positive with low PSMA expression defined by PSMA SUVmax < 10.
2. Previous history or presence of brain metastases or leptomeningeal metastases.
3. Any prior exposure to anti-PD-1, anti-PD-L1/L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathway.
4. Any prior treatment with cabazitaxel.
5. Any prior exposure to 177Lu-PSMA.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Patients with active, known or suspected autoimmune disease including Sjogren's syndrome. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible.
8. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
9. Participants must have recovered from all AEs due to previous therapies to =Grade 1 or baseline. Participants with = Grade 2 neuropathy may be eligible.
10. Patients with a condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids, and adrenal replacement doses = 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
11. Other malignancies within the previous 2-years other than, melanoma in situ, basal cell or squamous cell carcinomas of skin with a > 30% probability of recurrence within 12 months.
12. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
13. Patient has a known history of Human Immunodeficiency Virus (HIV).
14. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for = 4 weeks.
15. Previous history of interstitial lung disease or non-infectious pneumonitis.
16. Recent administration of a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
17. Recent administration of the influenza vaccine (within 30 days of registration).

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/12/2022
Sample size
Target
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Sydney
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Box Hill Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3128 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shahneen Sandhu
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03658447