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

NCT05340374 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 21/018
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Metastatic Castration-resistant Prostate Cancer; mCRPC

Outcome Measures

Primary Outcomes (3)

• Number of participants with Dose Limiting Toxicities (DLTs)

  A DLT is defined as a toxicity that prevents further administration of the trial treatment at that dose level. Each cohort of 3 patients be assessed for DLTs in the first 6 weeks (cycle 1) of treatment and a dose for the next cohort will be determined.

  Dose escalation phase is expected to be completed 9 months from the time the first patient is recruited.

• Maximum Tolerated dose (MTD)

  The MTD is defined as the highest dose level at which the incidence of DLT was less than 2/6.

  Dose escalation phase is expected to be completed 9 months from the time the first patient is recruited.

• Recommended Phase 2 Dose (RP2D)

  After the MTD is established, additional patients will be treated at the MTD. Safety and efficacy data from the study will be used to define the RP2D.

  Up to 30 months from the time the first patient is recruited.

Secondary Outcomes (9)

• Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Through study completion, up until 24 months after the last patient commences treatment

• 50% Prostate-Specific Antigen Response Rate (PSA-RR)

  Through study completion, up until 24 months after the last patient commences treatment

• Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST1.1) in patients with measurable disease

  Through study completion, up until 24 months after the last patient commences treatment

• Radiographic Progression-Free Survival (rPFS)

  Through study completion, up until 24 months after the last patient commences treatment

• PSA progression free survival (PSA-PFS)

  Through study completion, up until 24 months after the last patient commences treatment

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: Cabazitaxel; Drug: 177Lu-PSMA-617

Interventions

Cabazitaxel 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.

Treatment Arm

177Lu-PSMA-617 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.

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients aged 18 years or older at the time of informed consent.
• Patient has provided written informed consent.
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Patients must have had prior treatment with docetaxel.
• Patients must have progressed on a second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide) in the castrate-resistant setting.
• Patients must have progressive disease. The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines this 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
• Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
• Bone progression: ≥ 2 new lesions on bone scan
• At least three weeks since the completion of surgery prior to registration.
• Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
• Serum testosterone levels ≤ 1.75nmol/L within 28 days prior to registration.
• 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.
• Significant prostate-specific membrane antigen (PSMA) avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease.

You may not qualify if:

• Superscan on WBBS or diffuse marrow disease on PSMA PET.
• Site(s) of measurable disease that are FDG-positive with low PSMA expression (SUVmax \<10).
• Prior treatment with cabazitaxel or 177Lu-PSMA-617.
• Contraindications to the use of corticosteroid treatment.
• 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.
• Presence of untreated brain metastases or leptomeningeal metastases.
• Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
• Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
• Persistent toxicities (CTCAE v5.0 \>/= Grade 2) caused by previous cancer therapy, excluding alopecia.
• Known HIV or hepatitis B or C infection.
• Radiotherapy or systemic anti-cancer therapies administered within 14 days prior to registration, excluding androgen deprivation therapy (ADT).

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (2)

St Vincent's Hospital

Sydney, New South Wales, 2000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Interventions

cabazitaxel; Pluvicto

Study Officials

• A/Prof Arun Azad

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

• Prof Michael Hofman

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 22, 2022
• Study Start: July 14, 2022
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04

Locations

AU (2)