Safety and Targeting of Anti-hk2 Antibody in mCRPC

Study Overview
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Brief Summary
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This is an imaging trial, to develop h11B6 as a therapeutic radiopharmaceutical for men with mCRPC. This imaging study will be conducted to confirm the safety and estimate the mass amount of antibody h11B6, and confirm in vivo tumor targeting of the antibody, using Indium-111 (111In) radiolabeled h11B6 in subjects with advanced prostate cancer. This study will also provide the dosimetric information crucial for Phase 1 therapy.

Detailed Description
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It is the intent to develop h11B6 as a therapeutic radiopharmaceutical for men with mCRPC. This Phase 0 study will be conducted to confirm the safety, estimate the mass amount, and confirm in vivo tumor targeting of the antibody. This study will use Indium-111 (111In) radiolabeled h11B6 in subjects with mCRPC to image known sites of disease and identify a favorable mass amount of antibody for satisfactory tumor targeting with minimal/no accumulation off-target. In cohort 1, In-111 labeled h11B6 will remain fixed at 2 mg, and additional h11B6 will be added in 2 sub-cohorts (8 mg and 18 mg respectively); up to 6 patients may be entered into a sub-cohort. Additional patients (up to 6) will be studied once the most favorable mass and imaging time point have been established, to establish targeting of antibody to known disease. This study will provide the dosimetric information crucial for Phase 1 therapy.

Official Title
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A Phase 0 Study to Assess the Safety and Biodistribution of a Novel Radiolabeled Antibody Targeting Human Kallikrein-2 (hk2) in Subjects With Metastatic Castration-resistant Prostate Cancer.

Conditions
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Metastatic Disease, Castration-Resistant Prostatic Cancer

Intervention / Treatment
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* Drug: 111In-DOTA-h11B6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with mCRPC will be eligible if they meet the following criteria: Eastern Cooperative Oncology Group (ECOG) ≤ 1 Histologically or cytologically confirmed adenocarcinoma of the prostate Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L]) Metastatic disease documented by imaging Documented progressive mCRPC with androgen involvement as defined by - Prostate Cancer Working Group 3 Acceptable laboratory parameters At least 28 days since administration of any therapeutic radioactive isotope Able to tolerate the conditions required to perform imaging studies (e.g., lying flat for at least 1 hour). Exclusion Criteria: Known hypersensitivity to proteins, or other allergic diathesis that, in the opinion of the investigator, makes an immune response to humanized antibody likely Radiotherapy or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of study agent Any condition that, in the opinion of the Investigator, would impair the subject's ability to comply with study procedures and required study visits Active, symptomatic, or untreated brain metastases.

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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: 3-6 patients will be studied in each of 3 sub-cohorts to determine the most favorable mass amount of h11B6 (2 mg, 10 mg, 20 mg). An additional 6 patients will be imaged at the most favorable mass amount to assess tumor targeting.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dosimetry and targeting<br>Three sub-cohorts in cohort 1 will receive one slow bolus IV injection of 2 mg 111In-DOTA-h11B6 with 0, 8 and 18 mg unlabeled h11B6 respectively. In cohort 2, up to 6 patients will receive a slow bolus IV injection of 2 mg 111In-DOTA_h11B6 with any unlabeled h11B6 as determined from cohort 1, and will be imaged at one time-point | Drug: 111In-DOTA-h11B6<br>* 4-6 mCi 111In labeled to 2 mg DOTA-h11B6; 0, 8 or 18 mg additional h11B6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum pharmacokinetics | Serum clearance kinetics of 111In-DOTA-h11B6, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg). | 6 months | 
| Radioactivity Biodistribution | Radioactivity residence times in liver, kidneys and tumor, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg). | 6 months | 
| Radioactivity accumulation in known tumor sites | Number of known metastatic lesions in which there is increased uptake of 111In, in both cohorts 1 and 2. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, Radiolabeled antibody