A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find the highest dose level of study drug, CTT1403, that can be safely administered to patients with metastatic castration resistant prostate cancer (mCRPC).

Detailed Description
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This is a Phase 1, first-in-human dose escalation/dose expansion study evaluating escalating doses of CTT1403 in patients with PSMA-avid mCRPC with progressive disease on at least one androgen signaling inhibitor, followed by a dose expansion to further evaluate the safety, tolerability, efficacy and biological activity of CTT1403. CTT1403 is a PSMA-targeted 177Lu-labeled radiotherapy being developed for prostate cancer with a unique PSMA binding scaffold and an albumin binding moiety to extend circulation half-life. The PSMA binding scaffold is shared with CTT1057, a PSMA-specific PET diagnostic imaging agent shown in Phase 1 clinical trials to be specifically taken up by PSMA+ tumor. PSMA PET imaging by CTT1057 will be used diagnostically to select patients with PSMA-avid disease for treatment. The purpose of this study is to identify the dose limiting toxicity and recommended phase 2 dose of CTT1403. Eligible participants with demonstrated therapeutic benefit will be offered a second dose of study drug.

Official Title
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A Phase 1 Trial for Evaluation of Safety and 177Lu Radiation Dosimetry of CTT1403: A Peptidomimetic Inhibitor of Prostate Specific Membrane Antigen, in Metastatic Castration Resistant Prostate Cancer (mCRPC)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: CTT1403
* Drug: CTT1057
* Drug: 68Ga-PSMA-11


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed prostate adenocarcinoma that is metastatic and castration resistant (mCRPC). At least 3 metastatic foci avid for PSMA-specific PET agent (CTT1057) uptake on Screening PSMA PET. Has received docetaxol, ineligible for docetaxol, or refused docetaxol for the treatment of prostate cancer. Has progression by the PCWG3 criteria during or after treatment with either abiraterone or enzalutamide Male Age ≥ 18 years. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2). Demonstrate adequate organ function Exclusion Criteria: Has received previous treatment with radium-223 or another radiopharmaceutical within 3 months prior to first dose of CTT1403. Has received cabazitaxel for the treatment of mCRPC. Has received previous treatment with a therapeutic targeting PSMA. Has an additional active malignancy requiring therapy that may confound the assessment of the study endpoints. Has clinically significant cardiovascular disease Has a history of untreated brain metastases Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before CTT1403 administration. Has known positive status for chronic hepatitis B or hepatitis C Known or suspected myelodysplastic syndrome. Has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A-J<br>Patients with mCRPC and progressive disease on at least 1 androgen signaling inhibitor will be enrolled. | Drug: CTT1403<br>* Escalating doses of 0.75 GBq - 13.5 GBq will be administered in an accelerated to traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. Patients meeting eligibility criteria with demonstrated cessation of disease progression will be offered a second dose of the study drug, CTT1403.<br>Drug: CTT1057<br>* Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.<br>Drug: 68Ga-PSMA-11<br>* Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.<br>|
| Experimental: Cohort K - at Recommended Phase 2 Dose<br>Cohort F: Patients with mCRPC and progressive disease on at least 1 androgen signaling inhibitor will be enrolled at the recommended phase 2 dose. | Drug: CTT1403<br>* Escalating doses of 0.75 GBq - 13.5 GBq will be administered in an accelerated to traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. Patients meeting eligibility criteria with demonstrated cessation of disease progression will be offered a second dose of the study drug, CTT1403.<br>Drug: CTT1057<br>* Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.<br>Drug: 68Ga-PSMA-11<br>* Patients will be screened with CTT1057 or 68Ga-PSMA-11 PSMA PET to demonstrate presence of at least 3 PSMA avid lesions that can be targeted by the study drug, CTT1403. 5-7 weeks after administration of study drug, patients will be evaluated a second time with PSMA PET imaging using with either CTT1057 or 68Ga-PSMA-11 to assess potential efficacy of CTT1403.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of DLTs at escalating dose levels of CTT1403 |  | 6-8 weeks from time of injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of organ dosimetry of CTT1403 by SPECT/CT imaging at various time points |  | 6-8 weeks from time of injection | 
| Change from baseline in patient reported pain as measured by Brief Pain Index |  | up to 6 months after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET, lutetium, 177Lu, prostate cancer, metastatic castration resistant prostate cancer, prostate specific membrane antigen, mCRPC, PSMA, positron emission tomography, radiotherapy, targeted therapy