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Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection

Primary Purpose

Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, mCRPC

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
177Lu-rhPSMA-10.1 injection
18F-rhPSMA-7.3 injection
Sponsored by
Blue Earth Therapeutics Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring PSMA, mCRPC, Prostate cancer, 177Lu rhPSMA-10.1, 18F-rhPSMA-7.3, BET-PSMA-121, Blue Earth Therapeutics Limited, Radiohybrid, Radiopharmaceuticals

Eligibility Criteria

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

Inclusion Criteria:

  1. Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
  2. Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
  3. Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and full body 99mTc bone scan performed within 28 days of screening.
  4. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
  5. At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
  6. Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
  7. Prior major surgery must be at least 12 weeks prior to study entry.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
  9. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
  10. Adequate contraception for patients and their partners.
  11. Cohorts:

    1. Phase 1 and Phase 2 post-chemotherapy mCRPC
    2. Phase 2 taxane-naïve mCRPC

Exclusion Criteria:

  1. Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
  2. Presence of significant PSMA-negative disease on ceCT/MRI scan
  3. Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
  4. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
  5. Known history of haematological malignancy.
  6. Known history of central nervous system (CNS) metastases.
  7. Histological findings consistent with neuroendocrine phenotype of prostate cancer.
  8. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
  9. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
  10. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
  11. Ongoing treatment with bisphosphonates for bone-targeted therapy.
  12. Severe urinary incontinence that would preclude safe disposal of radioactive urine.
  13. Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator.
  14. Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
  15. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
  16. Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
  17. Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.

Sites / Locations

  • Washington University School of MedicineRecruiting
  • XCancer Omaha / Urology Cancer CenterRecruiting
  • Mount Sinai Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1, Cohort A

Phase 1, Cohort B

Phase 2, Cohort 1, post-chemotherapy mCRPC

Phase 2, Cohort 2, Taxane-naïve mCRPC

Arm Description

Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).

Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 2 cycles).

Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D]

Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D] .

Outcomes

Primary Outcome Measures

Phase 1 Incidence of DLTs
Incidence of DLTs during the DLT observation period.
Phase 1 Frequency and nature of TEAEs
Frequency and nature of treatment-emergent adverse events (TEAEs).
Phase 2, anti-tumour response
The number of subjects with an anti-tumour response defined as ≥50% reduction in PSA level from baseline.

Secondary Outcome Measures

Full Information

First Posted
May 20, 2022
Last Updated
September 8, 2023
Sponsor
Blue Earth Therapeutics Ltd
Collaborators
PSI CRO
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1. Study Identification

Unique Protocol Identification Number
NCT05413850
Brief Title
Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection
Official Title
An Open-label, Multicentre, Integrated Phase 1 & 2 Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Anti-tumour Activity of Lutetium (177Lu) rhPSMA-10.1 Injection in Men With Metastatic Castrate-resistant Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2022 (Actual)
Primary Completion Date
August 27, 2026 (Anticipated)
Study Completion Date
October 27, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Blue Earth Therapeutics Ltd
Collaborators
PSI CRO

4. Oversight

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

5. Study Description

Brief Summary
To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
Detailed Description
This is an interventional, non-randomised, open-label, integrated Phase 1 & 2 study to assess the safety, radiation dosing regimen and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 (Tx IMP) in men with metastatic castrate-resistant prostate cancer (mCRPC). The study will consist of 2 parts: a Phase 1, with safety, dose-finding, and dosimetry components, and a Phase 2, with assessment of efficacy and safety utilising the dose selected from Phase 1. Both phases will include subjects with prostate-specific membrane antigen (PSMA)-positive mCRPC as detected using 18F-rhPSMA-7.3 diagnostic IMP.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, mCRPC, Urogenital Neoplasms, Prostatic Neoplasms, Prostatic Diseases
Keywords
PSMA, mCRPC, Prostate cancer, 177Lu rhPSMA-10.1, 18F-rhPSMA-7.3, BET-PSMA-121, Blue Earth Therapeutics Limited, Radiohybrid, Radiopharmaceuticals

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1, Cohort A
Arm Type
Experimental
Arm Description
Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).
Arm Title
Phase 1, Cohort B
Arm Type
Experimental
Arm Description
Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 2 cycles).
Arm Title
Phase 2, Cohort 1, post-chemotherapy mCRPC
Arm Type
Experimental
Arm Description
Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D]
Arm Title
Phase 2, Cohort 2, Taxane-naïve mCRPC
Arm Type
Experimental
Arm Description
Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D] .
Intervention Type
Drug
Intervention Name(s)
177Lu-rhPSMA-10.1 injection
Other Intervention Name(s)
177Lu-rhPSMA-10.1
Intervention Description
Therapeutic cycles of 177Lu-rhPSMA-10.1
Intervention Type
Diagnostic Test
Intervention Name(s)
18F-rhPSMA-7.3 injection
Other Intervention Name(s)
18F-rhPSMA-7.3
Intervention Description
18F-rhPSMA-7.3 at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.
Primary Outcome Measure Information:
Title
Phase 1 Incidence of DLTs
Description
Incidence of DLTs during the DLT observation period.
Time Frame
6 weeks post final IMP
Title
Phase 1 Frequency and nature of TEAEs
Description
Frequency and nature of treatment-emergent adverse events (TEAEs).
Time Frame
End of study
Title
Phase 2, anti-tumour response
Description
The number of subjects with an anti-tumour response defined as ≥50% reduction in PSA level from baseline.
Time Frame
12 weekly intervals

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate. Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration. Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and full body 99mTc bone scan performed within 28 days of screening. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan. At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH). Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed). Prior major surgery must be at least 12 weeks prior to study entry. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline. Adequate contraception for patients and their partners. Cohorts: Phase 1 and Phase 2 post-chemotherapy mCRPC Phase 2 taxane-naïve mCRPC Exclusion Criteria: Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents. Presence of significant PSMA-negative disease on ceCT/MRI scan Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan). Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression. Known history of haematological malignancy. Known history of central nervous system (CNS) metastases. Histological findings consistent with neuroendocrine phenotype of prostate cancer. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results. Ongoing treatment with bisphosphonates for bone-targeted therapy. Severe urinary incontinence that would preclude safe disposal of radioactive urine. Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator. Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys. Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation. Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Blue Earth Therapeutics
Phone
+44 (0)1865 634500
Email
contact@blueearthTx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Blue Earth Therapeutics
Organizational Affiliation
Blue Earth Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Kim, MD
Phone
314-362-8567
Email
kim.hyun@wustl.edu
Facility Name
XCancer Omaha / Urology Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nordquist
Phone
402-991-8468
Email
drnordquist@gucancer.com
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Munir Ghesani, MD
Phone
212-241-7888
Email
Munir.Ghesani@mountsinai.org

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.blueearththerapeutics.com
Description
Sponsor website

Learn more about this trial

Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection

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