search
Back to results

A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (TheraP)

Primary Purpose

Cancer of the Prostate, Metastatic Cancer

Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
177Lu-PSMA617
Cabazitaxel
Sponsored by
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer of the Prostate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by:

    • Documented histopathology of prostate adenocarcinoma OR
    • Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes)
  2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog
  3. Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL
  4. Target or non-target lesions according to RECIST 1.1
  5. Prior treatment with docetaxel
  6. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
  7. ECOG Performance status 0 to 2
  8. Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel

  9. Adequate renal function:

    • Cr Cl ≥ 40mL/min (Cockcroft-Gault formula)

  10. Adequate bone marrow function:

    • Platelets ≥ 100 x10 billion /L
    • Hb ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
    • Neutrophils > 1.5 x10 billion/L

  11. Adequate liver function:

    • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5-2x ULN, must have a normal conjugated bilirubin)
    • AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
  12. Estimated life expectancy > 12 weeks
  13. Study treatment both planned and able to start within 21 days of randomisation
  14. Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments
  15. Signed, written informed consent

Exclusion Criteria:

  1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
  2. Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10
  3. Sjogren's syndrome
  4. Prior treatment with cabazitaxel or Lu-PSMA
  5. Contraindications to the use of corticosteroid treatment
  6. Active malignancy other than prostate cancer
  7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
  8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
  9. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Sites / Locations

  • Liverpool Hospital
  • St Vincent's Hospital
  • Royal North Shore Hospital
  • Calvary Mater Newcastle Hospital
  • Royal Brisbane and Womens Hospital
  • Royal Adelaide Hospital
  • Peter MacCallum Cancer Centre
  • Austin Hospital
  • Monash Moorabbin Hospital
  • Fiona Stanley Hospital
  • Sir Charles Gairdner Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

177Lu-PSMA617

Cabazitaxel

Arm Description

Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.

Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles. Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.

Outcomes

Primary Outcome Measures

Prostate Specific Antigen response rate (PSA RR)
PSA RR defined as the proportion of participants in each group with a PSA reduction of ≥ 50% from baseline.

Secondary Outcome Measures

Pain Response (PPI and Analgesic Score)
Pain response rate, defined as: >=2 point reduction in PPI score from baseline with no increase in analgesic score; and/or >=50% decrease in analgesic score with no increase in PPI PPI: McGill-Melzack Present Pain Intensity Scale (PPI) Analgesic score: Using Morphine Equivalent Daily Dose (MEDD)
Objective Tumour Response Rate
Objective Tumour Response Rate - defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) divided by the total number of participants (using RECIST 1.1).
Progression free survival
Progression free survival - the time from randomisation to date of PSA progression (blood samples), pain progression (on PPI) or radiographic progression (PCWG3 for bone and RECIST 1.1 for soft tissue), whichever occurs first
PSA progression free survival
PSA progression free survival, defined as the time from randomisation to PSA progression, assessed using PCWG3 criteria on blood test results.
Pain progression free survival
Pain progression free survival - defined as the time from randomisation to pain progression (>=1 point increase on PPI from nadir and >=25% increase in analgesic score (MEDD) from nadir, OR need for palliative radiotherapy).
Radiographic progression free survival
Radiographic progression free survival - defined as the time from randomisation to radiographic progression (assessed using PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions).
Health-related quality of life
Health-related quality of life, assessed using a composite of the EORTC core quality of life questionnaire (QLQ C-30) and the Patient Disease and Treatment Assessment Form (PDF).
Overall survival
Overall survival - time from registration to death from any cause or last known follow-up alive.
Frequency and severity of adverse events
Frequency and severity of adverse events (composite), assessed using CTCAE v4.03.

Full Information

First Posted
December 11, 2017
Last Updated
June 9, 2022
Sponsor
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Collaborators
Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, Prostate Cancer Foundation of Australia (PCFA), Australasian Radiopharmaceutical Trials network (ARTnet), Movember Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT03392428
Brief Title
A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer
Acronym
TheraP
Official Title
TheraP: A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (ANZUP Protocol 1603)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
January 29, 2018 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Collaborators
Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, Prostate Cancer Foundation of Australia (PCFA), Australasian Radiopharmaceutical Trials network (ARTnet), Movember Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This open label, randomised, stratified, 2-arm, multicentre, phase 2 trial aims to determine the activity and safety of Lu-PSMA vs cabazitaxel in men with progressive metastatic castration resistant prostate cancer
Detailed Description
Despite recent advances in the treatment of prostate cancer, metastatic disease remains incurable. Prostate specific membrane antigen (PSMA) is present in high quantities on the cell surface of prostate cancers, and is also further increased in metastatic hormone refractory carcinomas. PSMA is an attractive target for both imaging and treatment of prostate cancer. PSMA bound to the radioactive substance Gallium68 (GaPSMA) is rapidly being adopted for imaging prostate cancer using positron emission tomography (PET) scanning. Radionuclide therapy is an approach for the treatment of cancer that uses tumour targeting agents to deliver high doses of radiation to sites of tumours. The PSMA molecule used for PET imaging can also be labelled with Lutetium177 (Lu177), a radioactive substance. The aim of this study is to determine the activity and safety of LuPSMA radionuclide therapy. Patients with metastatic prostate cancer who have progressed despite hormonal therapy and chemotherapy, will be randomised to receive either LuPSMA radionuclide therapy (up to a maximum of 6 cycles of therapy) or cabazitaxel chemotherapy (up to a maximum of 10 cycles of therapy). 200 participants will be recruited from sites across Australia. The study will determine the effects on PSA response rate (primary endpoint), pain response, progression free survival, quality of life, and frequency and severity of adverse events. Correlative outcomes include associations between PET imaging and clinical outcomes, and biomarkers and clinical outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of the Prostate, Metastatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Open label, randomised, stratified, 2-arm, phase 2 trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
201 (Actual)

8. Arms, Groups, and Interventions

Arm Title
177Lu-PSMA617
Arm Type
Experimental
Arm Description
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.
Arm Title
Cabazitaxel
Arm Type
Active Comparator
Arm Description
Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles. Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.
Intervention Type
Other
Intervention Name(s)
177Lu-PSMA617
Other Intervention Name(s)
Lutetium Prostate-specific membrane antigen
Intervention Description
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel
Other Intervention Name(s)
Jevtana
Intervention Description
Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles. Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.
Primary Outcome Measure Information:
Title
Prostate Specific Antigen response rate (PSA RR)
Description
PSA RR defined as the proportion of participants in each group with a PSA reduction of ≥ 50% from baseline.
Time Frame
Through study completion, on average 4 years
Secondary Outcome Measure Information:
Title
Pain Response (PPI and Analgesic Score)
Description
Pain response rate, defined as: >=2 point reduction in PPI score from baseline with no increase in analgesic score; and/or >=50% decrease in analgesic score with no increase in PPI PPI: McGill-Melzack Present Pain Intensity Scale (PPI) Analgesic score: Using Morphine Equivalent Daily Dose (MEDD)
Time Frame
Through study completion, on average 4 years
Title
Objective Tumour Response Rate
Description
Objective Tumour Response Rate - defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) divided by the total number of participants (using RECIST 1.1).
Time Frame
Through study completion, on average 4 years
Title
Progression free survival
Description
Progression free survival - the time from randomisation to date of PSA progression (blood samples), pain progression (on PPI) or radiographic progression (PCWG3 for bone and RECIST 1.1 for soft tissue), whichever occurs first
Time Frame
Through study completion, on average 4 years
Title
PSA progression free survival
Description
PSA progression free survival, defined as the time from randomisation to PSA progression, assessed using PCWG3 criteria on blood test results.
Time Frame
Through study completion, on average 4 years
Title
Pain progression free survival
Description
Pain progression free survival - defined as the time from randomisation to pain progression (>=1 point increase on PPI from nadir and >=25% increase in analgesic score (MEDD) from nadir, OR need for palliative radiotherapy).
Time Frame
Through study completion, on average 4 years
Title
Radiographic progression free survival
Description
Radiographic progression free survival - defined as the time from randomisation to radiographic progression (assessed using PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions).
Time Frame
Through study completion, on average 4 years
Title
Health-related quality of life
Description
Health-related quality of life, assessed using a composite of the EORTC core quality of life questionnaire (QLQ C-30) and the Patient Disease and Treatment Assessment Form (PDF).
Time Frame
Through study completion, on average 4 years
Title
Overall survival
Description
Overall survival - time from registration to death from any cause or last known follow-up alive.
Time Frame
Through study completion, on average 4 years
Title
Frequency and severity of adverse events
Description
Frequency and severity of adverse events (composite), assessed using CTCAE v4.03.
Time Frame
From first study dose to 12 weeks after completing study treatment
Other Pre-specified Outcome Measures:
Title
Tertiary Correlative objectives: Associations between Ga-68 PSMA PET/CT, FDG-PET/CT baseline characteristics, and outcomes
Description
Identification of Ga-68 PSMA PET/CT, FDG-PET/CT markers to predict outcomes.
Time Frame
Through study completion, on average 4 years
Title
Tertiary Correlative objectives: Associations between clinical outcomes and possible prognostic and/or predictive biomarkers (tissue and circulating) including ctDNA
Description
Identification of biomarkers to predict outcomes.
Time Frame
Through study completion, on average 4 years

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
This study is looking at prostate cancer which only affects males. The prostate gland is a male reproductive organ
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by: Documented histopathology of prostate adenocarcinoma OR Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL Target or non-target lesions according to RECIST 1.1 Prior treatment with docetaxel Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) ECOG Performance status 0 to 2 Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel Adequate renal function: • Cr Cl ≥ 40mL/min (Cockcroft-Gault formula) Adequate bone marrow function: Platelets ≥ 100 x10 billion /L Hb ≥ 90g/L (no red blood cell transfusion in last 4 weeks) Neutrophils > 1.5 x10 billion/L Adequate liver function: Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5-2x ULN, must have a normal conjugated bilirubin) AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases) Estimated life expectancy > 12 weeks Study treatment both planned and able to start within 21 days of randomisation Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments Signed, written informed consent Exclusion Criteria: Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10 Sjogren's syndrome Prior treatment with cabazitaxel or Lu-PSMA Contraindications to the use of corticosteroid treatment Active malignancy other than prostate cancer Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Hofman, A/Prof
Organizational Affiliation
Peter MacCallum Cancer Centre, Melbourne, Australia
Official's Role
Study Chair
Facility Information:
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
St Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Royal North Shore Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Calvary Mater Newcastle Hospital
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Royal Brisbane and Womens Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3008
Country
Australia
Facility Name
Austin Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Monash Moorabbin Hospital
City
Moorabbin
State/Province
Victoria
ZIP/Postal Code
3165
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6450
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
36350899
Citation
Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon HM, Davis ID, Ralph N. Experiences of participants in a clinical trial of a novel radioactive treatment for advanced prostate cancer: A nested, qualitative longitudinal study. PLoS One. 2022 Nov 9;17(11):e0276063. doi: 10.1371/journal.pone.0276063. eCollection 2022.
Results Reference
derived
PubMed Identifier
36261050
Citation
Buteau JP, Martin AJ, Emmett L, Iravani A, Sandhu S, Joshua AM, Francis RJ, Zhang AY, Scott AM, Lee ST, Azad AA, McJannett MM, Stockler MR, Williams SG, Davis ID, Hofman MS; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol. 2022 Nov;23(11):1389-1397. doi: 10.1016/S1470-2045(22)00605-2. Epub 2022 Oct 16.
Results Reference
derived
PubMed Identifier
34373282
Citation
Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon H, Davis ID, Ralph N. Advanced prostate cancer experimental radioactive treatment-clinical trial decision making: patient experiences. BMJ Support Palliat Care. 2021 Aug 9:bmjspcare-2021-002994. doi: 10.1136/bmjspcare-2021-002994. Online ahead of print.
Results Reference
derived
PubMed Identifier
33581798
Citation
Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3. Epub 2021 Feb 11.
Results Reference
derived
PubMed Identifier
31595044
Citation
Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.
Results Reference
derived

Learn more about this trial

A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer

We'll reach out to this number within 24 hrs