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177Lu-PSMA-617 Therapy and Olaparib in Patients With Metastatic Castration Resistant Prostate Cancer
This phase 1 dose-escalation and dose-expansion study is designed to evaluate the safety and tolerability of olaparib in combination with 177Lutetium-Prostate Specific Membrane Antigen (177 Lu-PSMA) in patients with metastatic castration resistant prostate cancer (mCRPC).
Study details:
This phase 1, open label, multicentre, dose-escalation and dose-expansion study is designed to evaluate the safety and tolerability of olaparib in combination with 177Lu-PSMA in patients with mCRPC. Patients with mCRPC who have previously progressed on a novel AR targeted agent (abiraterone and/or enzalutamide and/or apalutamide) and have not had prior exposure to platinums, PARP inhibitors or 177Lu-PSMA will be eligible for the study. Patients can have had prior exposure to docetaxel in the chemotherapy naïve setting or castrate setting.
Patients will be enrolled in two stages: a dose escalation and a dose expansion phase. The clinical and translational outcomes from this study will inform the design of future phase 2/3 clinical trials of this combination. This is a single arm study where patients will receive 177Lu-PSMA and olaparib for up to 6 cycles.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: Male
Things to know
Study dates
Study start: 2019-07-09
Primary completion: 2025-05-01
Study completion finish: 2026-06-01
Study type
TREATMENT
Phase
PHASE1
Trial ID
NCT03874884
Intervention or treatment
DRUG: Olaparib
COMBINATION_PRODUCT: 177Lu-PSMA
Conditions
- • Metastatic Castration Resistant Prostate Cancer (mCRPC)
Find a site
Closest Location:
St Vincent's Hospital Sydney
Research sites nearby
Select from list below to view details:
St Vincent's Hospital Sydney
Sydney, New South Wales, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: 177Lu-PSMA + olaparib
| DRUG: Olaparib
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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 11 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 11 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. | Upto 30 months from the time the first patient is recruited. |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. | Safety of the combination will be measured by AEs and SAEs. | Through study completion, up until 18 months after the last patient commences treatment. |
Radiographic progression-free survival (rPFS) | rPFS is defined as the time from treatment initiation to the first date of documented radiographic progression using conventional imaging or death due to any cause, whichever occurs first. The radiographic progression will be assessed by the investigator per RECIST1.1 for soft tissue and PCWG3 for bone lesions. | Through study completion, up until 18 months after the last patient commences treatment. |
PSA progression free survival (PSA-PFS) | PSA-PFS is defined as the time from treatment initiation to the date of PSA progression per PCWG3 or death due to any cause, whichever occurs first. The date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2ng/mL or more from the nadir is documented. For patients who have an initial PSA decline during treatment, this must be confirmed by a second value 3 or more weeks later. | Through study completion, up until 18 months after the last patient commences treatment. |
Objective response rate (ORR) by RECIST1.1 in patients with measurable disease | Objective Response (OR) is only applicable for the subset of patients with measurable disease by RECIST1.1. OR is defined as a partial response (PR) or complete response (CR) at any stage from time of commencement of protocol treatment to the time of subsequent systemic anti-cancer treatment. The ORR is calculated as the proportion of patients with a best response of CR or PR. | Through study completion, up until 18 months after the last patient commences treatment. |
Overall survival (OS) | OS is defined as the time from treatment initiation to the date of death due to any cause. | Through study completion, up until 18 months after the last patient commences treatment. |
50% PSA response rate (PSA-RR) | PSA will be assessed at baseline and every 6 weeks from cycle 1 day 1 independent of olaparib and 177Lu-PSMA dosing. PSA response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response. | Through study completion, up until 78 weeks after the last patient commences treatment. |
Duration of response (DOR) | DOR-PCWG3 is defined as the time between the date of first response (CR/PR per RECIST1.1 for soft tissue and PCWG3 for bone lesions) to the date of first documented radiographic progression per RECIST1.1 for soft tissue and PCWG3 for bone lesions or cancer-related death. | Through study completion, up until 18 months after the last patient commences treatment. |
Time to treatment response (TTR) in the subset of patients who achieved a 50% PSA response | TTR-PCWG3 is defined as the time from treatment initiation to the date of the first documented CR or PR per RECIST1.1 for soft tissue and PCWG3 for bone lesions. | Through study completion, up until 18 months after the last patient commences treatment. |
Treatment discontinuation due to toxicity | The number of patients who discontinue treatment at any time due to treatment related toxicity (yes/no for each patient) will be reported. | Through study completion, up until 18 months after the last patient commences treatment. |
Rate of treatment discontinuation due to toxicity | The percentage of patients who discontinue treatment due to treatment related toxicity will be reported. | Through study completion, up until 18 months after the last patient commences treatment. |
Frequently Asked Questions
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