Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer

NCT ID: NCT05340374

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-14
• Study Completion Date: 2026-12-31

Brief Summary

This clinical trial will evaluate the safety of Cabazitaxel in combination with 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

Detailed Description

This prospective, single-centre, single-arm, open label, phase I/II trial will assess the safety, efficacy and anti-tumour activity of cabazitaxel in combination with 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC).

This study aims to assess and establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of cabazitaxel in combination with 177Lu-PSMA-617 in patients with mCRPC.

32-44 men with mCRPC who have progressed on prior docetaxel and a second-generation AR antagonist will be enrolled in this trial in two stages: dose escalation and a dose expansion phase over a period of 18 months.

Conditions

Metastatic Castration-resistant Prostate Cancer; mCRPC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cabazitaxel

Intervention Type: DRUG

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.

177Lu-PSMA-617

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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 Type: DRUG

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A/Prof Arun Azad

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Prof Michael Hofman

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Locations

St Vincent's Hospital

Sydney, New South Wales, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

21/018

Identifier Type: -

Identifier Source: org_study_id