38 Participants Needed

SAR-BBN Radiotracers for Prostate Cancer

(COMBAT Trial)

Recruiting at 7 trial locations
CP
Overseen ByClarity Pharmaceuticals
Age: 18+
Sex: Male
Trial Phase: Phase 1 & 2
Sponsor: Clarity Pharmaceuticals Ltd
Must be taking: Androgen deprivation
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The aim for this study is to determine the safety and efficacy of 67Cu-SAR-BBN in participants with Gastrin Releasing Peptide Receptor (GRPR)-expressing metastatic castrate resistant prostate cancer in patients who are ineligible for therapy with 177Lu-PSMA-617.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic anti-cancer therapy must be stopped at least 4 weeks before starting the trial, except for specific hormone therapies and low-dose corticosteroids.

What data supports the effectiveness of the treatment 64Cu-SAR-BBN for prostate cancer?

Research shows that copper-64 (64Cu) is effective in imaging and potentially treating prostate cancer due to its ability to target specific receptors on cancer cells. In a study, a similar treatment using copper-67 (67Cu) significantly inhibited tumor growth in mice, suggesting that copper-based treatments like 64Cu-SAR-BBN could be promising for prostate cancer.12345

Is 64Cu-SAR-BBN safe for use in humans?

In a Phase I trial involving 64Cu-SAR-BBN PET-CT imaging for breast cancer, no adverse events were reported, suggesting it is generally safe for human use.23456

What makes the SAR-BBN radiotracers unique for prostate cancer treatment?

The SAR-BBN radiotracers, using copper isotopes like 64Cu and 67Cu, are unique because they target the gastrin-releasing peptide receptor (GRPR) which is overexpressed in prostate cancer cells, allowing for both precise imaging and targeted therapy. This dual capability, known as theranostics, enables the same compound to be used for both diagnosing and treating cancer, which is not common in many existing treatments.23456

Research Team

CP

Clarity Pharmaceuticals

Principal Investigator

Clarity Pharmaceuticals

Eligibility Criteria

This trial is for adults with metastatic castrate resistant prostate cancer that expresses GRPR, who can't have 177Lu-PSMA-617 therapy. They must have good kidney function, progressive bone disease visible on scans, and a positive PET/CT scan with 64Cu-SAR-BBN. Participants need to be ineligible for certain other treatments and recovered from previous therapies' side effects.

Inclusion Criteria

Have progressive metastatic castration-resistant prostate cancer (mCRPC) despite prior androgen deprivation therapy (ADT) and at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors). Documented progressive mCRPC will be based on at least 1 of the following criteria: Serum/plasma prostate specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal value for study enrollment is 2.0 ng/mL; Soft-tissue progression defined as a ≥20% increase in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since the last treatment directed at the metastatic cancer has started (not including hormonal therapy) or the appearance of 1 or more new lesions; Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan. Participants must be ineligible for 177Lu-PSMA-617 therapy based on the following criterion: Uptake of 68Ga-PSMA-11 or 18F-DCFPyL in all lesions is negative (equal to or lower than that of liver parenchyma), or any one lesion larger than the size criteria is negative [size criteria: organs ≥1 cm, lymph nodes ≥2.5 cm, bones(soft tissue component) ≥1 cm]. Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (prior chemotherapy, radiation, immunotherapy, etc.); Participants must have adequate organ function: Bone marrow reserve: White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 109/L is equivalent to 2.5 x 103/μL and 2.5 x K/μL and 2.5 x 103/cc and 2500/μL) OR Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1.5 x 109 /L is equivalent to 1.5 x 103 /μL and 1.5 x K/μL and 1.5 x 103 /cc and 1500/μL); Platelets ≥100 x 109 /L (100 x 109 /L is equivalent to 100 x 103 /μL and 100 x K/μL and 100 x 103 /cc and 100,000/μL); Hemoglobin ≥9 g/dL (5.59 mmol/L); Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted; Alanine aminotransferase or aspartate aminotransferase ≤3.0 x ULN OR ≤5.0 x ULN for participants with liver metastases; Estimated glomerular filtration rate (eGFR) ≥50 mL/min For participants who are human immunodeficiency virus infected: Participant must be healthy and have a low risk of Acquired Immune Deficiency Syndrome related outcomes in the opinion of the Investigator; For participants who have partners of childbearing potential: Partner and/or participant must use a method of birth control with adequate barrier protection.
My prostate cancer diagnosis was confirmed through lab tests.
I have at least one cancer spread that shows on recent scans.
See 6 more

Exclusion Criteria

Previous treatment with any investigational agents within 4 weeks prior enrollment into the study
I was diagnosed with a blood clot in my leg or lung in the last 4 weeks.
My prostate cancer is of the small cell type.
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive up to 2 administrations of 64Cu-SAR-BBN and single or multiple administrations of 67Cu-SAR-BBN based on cohort allocation

Up to 8 weeks

Cohort Expansion

Participants receive up to 3 administrations of 64Cu-SAR-BBN and 2 administrations of 67Cu-SAR-BBN at the recommended dose level

Up to 14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

  • 64Cu-SAR-BBN
  • 67Cu-SAR-BBN
Trial OverviewThe study tests the safety and effectiveness of two radioactive drugs, 64Cu-SAR-BBN and 67Cu-SAR-BBN, in targeting GRPR-expressing prostate cancer cells in patients who cannot receive another specific treatment (177Lu-PSMA-617).
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 67Cu-SAR-BBNExperimental Treatment2 Interventions
In the dose escalation phase: 64Cu-SAR-BBN: Patients will receive up to 2 administrations of 200MBq 67Cu-SAR-BBN: Cohorts 1 - 3: Single administration (dose will be determined based on cohort allocation). Cohort 4: 2 administrations at the recommended dose (determined by cohorts 1-3). In the cohort expansion phase: Patients will receive up to 3 administrations of 200MBq of 64Cu-SAR-BBN and 2 administrations at the recommended dose level of 67Cu-SAR-BBN, determined through the dose escalation. Additional administrations: (up to a maximum total of 4) may be offered to those participants, in either the dose escalation or cohort expansion, with radiological non-progression.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Clarity Pharmaceuticals Ltd

Lead Sponsor

Trials
11
Recruited
720+

Findings from Research

Copper-64 (64Cu) is a promising PET/CT tracer for diagnosing various cancers, including prostate cancer and glioblastoma, due to its ability to target copper-avid tumors and its favorable nuclear properties for both imaging and therapy.
Studies indicate that 64CuCl2 is safe in terms of radiation and toxicology, making it a viable option for theragnostic applications in oncology, particularly for imaging and potentially treating cancers like hepatocellular carcinoma and malignant melanoma.
Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent.Capriotti, G., Piccardo, A., Giovannelli, E., et al.[2023]
The study demonstrated that the targeted copper theranostic agent [67Cu]Cu-SAR-BBN effectively binds to GRPR-positive prostate cancer cells, achieving over 52% binding, which is significantly higher than the control.
In a pre-clinical mouse model, treatment with [67Cu]Cu-SAR-BBN resulted in a remarkable 93.3% inhibition of tumor growth and increased median survival from 34.5 days in the control group to over 54 days, indicating strong therapeutic efficacy.
Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer.Huynh, TT., van Dam, EM., Sreekumar, S., et al.[2023]
The study shows that the CB-TE2A chelation system significantly improves the in vivo stability and clearance of 64Cu bombesin analogs in a prostate cancer mouse model, leading to better targeting of the BB2 receptor with reduced nontarget retention.
In comparison to the DOTA chelation system, the CB-TE2A system resulted in lower liver uptake and higher overall clearance of the radioconjugate, indicating its potential for enhanced safety and efficacy in diagnostic imaging and therapy.
In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems.Garrison, JC., Rold, TL., Sieckman, GL., et al.[2016]

References

Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. [2023]
Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer. [2023]
In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. [2016]
64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial. [2023]
The emerging value of 64Cu for molecular imaging and therapy. [2021]
Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [64Cu-NO2A-(X)-BBN(7-14)NH2], in a prostate tumor xenografted mouse model. [2019]