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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05340374




Registration number
NCT05340374
Ethics application status
Date submitted
14/04/2022
Date registered
22/04/2022
Date last updated
27/11/2023

Titles & IDs
Public title
Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer
Scientific title
Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer
Secondary ID [1] 0 0
21/018
Universal Trial Number (UTN)
Trial acronym
LuCAB
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabazitaxel
Treatment: Drugs - 177Lu-PSMA-617

Experimental: Treatment Arm - In this single-arm study, patients will receive 7.4 GBq of 177Lu-PSMA-617 on Day 1 of every 6 week Cycle. Cabazitaxel will be administered concurrently on Day 2 and Day 23 of each Cycle (every 3 weeks). The dose of cabazitaxel will vary in dose-escalation. Up to 6 Cycles will be given.


Treatment: Drugs: Cabazitaxel
Cabazitaxel belongs to the Taxane group of drugs which function by interfering with microtubule depolymerisation and thus inhibit mitosis, which leads to cell death via apoptosis. It is the first chemotherapy agent to improve survival in patients with mCRPC with progressive disease after docetaxel-based treatment.

Treatment: Drugs: 177Lu-PSMA-617
Lutetium-177 (177Lu)-PSMA is a radiopharmaceutical comprised of a small molecule inhibitor of PSMA that binds with high affinity to PSMA which is expressed on the prostate cancer cell, labelled with 177Lu. 177Lu has favourable characteristics for radionuclide therapy emitting both a short-range (1-2mm) cytotoxic beta-particle, minimising irradiation of non-targeted normal tissues, alongside gamma emission that allows imaging. Multiple clinical trials have demonstrated high clinical activity and limited normal tissue toxicity using 177Lu-PSMA-617.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Dose escalation phase is expected to be completed 9 months from the time the first patient is recruited.
Primary outcome [2] 0 0
Maximum Tolerated dose (MTD)
Timepoint [2] 0 0
Dose escalation phase is expected to be completed 9 months from the time the first patient is recruited.
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [3] 0 0
Up to 30 months from the time the first patient is recruited.
Secondary outcome [1] 0 0
Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Timepoint [1] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [2] 0 0
50% Prostate-Specific Antigen Response Rate (PSA-RR)
Timepoint [2] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [3] 0 0
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST1.1) in patients with measurable disease
Timepoint [3] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [4] 0 0
Radiographic Progression-Free Survival (rPFS)
Timepoint [4] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [5] 0 0
PSA progression free survival (PSA-PFS)
Timepoint [5] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [6] 0 0
Overall survival (OS)
Timepoint [6] 0 0
Through study completion, up until 24 months after the last patient commences treatment
Secondary outcome [7] 0 0
Describe pain within 12 months of treatment commencement
Timepoint [7] 0 0
Through completion of 12 months after treatment commencement of last patient
Secondary outcome [8] 0 0
Describe health-related quality of life (QoL) within 12 months of treatment commencement
Timepoint [8] 0 0
Through completion of 12 months after treatment commencement of last patient
Secondary outcome [9] 0 0
Rate of treatment discontinuation due to toxicity
Timepoint [9] 0 0
Through study completion, up until 24 months after the last patient commences treatment

Eligibility
Key inclusion criteria
1. Male patients aged 18 years or older at the time of informed consent.
2. Patient has provided written informed consent.
3. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
4. Eastern Cooperative Oncology Group (ECOG) performance status of = 1
5. Patients must have had prior treatment with docetaxel.
6. Patients must have progressed on a second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide) in the castrate-resistant setting.
7. Patients must have progressive disease. The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines this as any one of the following:

1. PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of = 1 week between each measurement
2. Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
3. Bone progression: = 2 new lesions on bone scan
8. At least three weeks since the completion of surgery prior to registration.
9. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
10. Serum testosterone levels = 1.75nmol/L within 28 days prior to registration.
11. Imaging evidence of metastatic disease documented with either whole body bone scan (WBBS) or computed tomography (CT) scan performed within 28 days prior to registration.
12. Significant prostate-specific membrane antigen (PSMA) avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease.
13. Patients must have a life expectancy = 12 weeks.
14. Assessed by a medical oncologist as suitable for treatment with cabazitaxel and 177Lu-PSMA-617.
15. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:

1. Haemoglobin = 90 g/L independent of transfusions (no red blood cell transfusion in last 28 days prior to registration)
2. Absolute neutrophil count (ANC) = 1.5x10^9/L
3. Platelets = 150 x10^9/L
4. Total bilirubin = 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
5. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN if there is no evidence of liver metastasis or = 5 x ULN in the presence of liver metastases
6. Albumin = 25 g/L
7. Adequate renal function: patients must have a creatinine clearance estimated of = 40 mL/min using the Cockcroft-Gault equation
16. Sexually active patients are willing to use medically acceptable forms of barrier contraception.
17. Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Superscan on WBBS or diffuse marrow disease on PSMA PET.
2. Site(s) of measurable disease that are FDG-positive with low PSMA expression (SUVmax <10).
3. Prior treatment with cabazitaxel or 177Lu-PSMA-617.
4. Contraindications to the use of corticosteroid treatment.
5. Other malignancies within the previous 2-years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
6. Presence of untreated brain metastases or leptomeningeal metastases.
7. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for = four weeks.
8. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
9. Persistent toxicities (CTCAE v5.0 >/= Grade 2) caused by previous cancer therapy, excluding alopecia.
10. Known HIV or hepatitis B or C infection.
11. Radiotherapy or systemic anti-cancer therapies administered within 14 days prior to registration, excluding androgen deprivation therapy (ADT).

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - 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
A/Prof Arun Azad
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
Gaurav Sharma
Address 0 0
Country 0 0
Phone 0 0
03 85596830
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


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.