Treatment With Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find out how effective 177Lu -J591 is in the treatment of patients with metastatic, androgen-independent prostate cancer.

Detailed Description
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To determine the clinical activity of 177Lu -J591 for the treatment of patients with metastatic, androgen-independent prostate cancer. Patients will receive a single dose of J591 (total antibody of 20 mg) consisting of antibody chelated with 177Lu at a dose of 65 or 70 mCi/m2 with a specific activity of 12-15 mCi/mg plus non-radiolabeled antibody.

Official Title
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A Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Androgen-Independent Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: 177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu -J591)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of prostate adenocarcinoma. Metastatic prostate cancer progressive on imaging studies and/or rising PSA despite adequate medical or surgical castration therapy. Progressed following discontinuation of anti-androgen therapy, if received. Serum testosterone < 50 ng/ml Exclusion Criteria: Use of corticosteroids and/or adrenal hormone inhibitors within 4 weeks of treatment. Use of PC-SPES within 4 weeks of treatment. Use of red blood cell or platelet transfusions within 4 weeks of treatment. Use of hematopoietic growth factors within 4 weeks of treatment. Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment. Bone scan demonstrating confluent lesions involving both axial and appendicular skeleton. Prior radiation therapy encompassing >25% of skeleton. Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®, Quadramet®). Active angina pectoris or NY Heart Association Class III-IV. History of deep vein thrombophlebitis and/or pulmonary embolus within 3 months of study entry. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study. Prior monoclonal antibody therapy with the exception of ProstaScint® Prior investigational therapy (medications or devices) within 6 weeks of treatment. Known history of HIV

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>Eligible patients will receive a single dose of 177Lu-J591 (65 or 70 mCi/m2) consisting of J591 chelated at a specific activity of 12-15 mCi of 177Lu per mg of antibody plus sufficient non-radiolabeled, non-DOTA-conjugated (naked) J591 to achieve a total antibody dose of 20 mg. Each dose will be administered by an IV infusion at a rate not to exceed 5 mg/min. | Drug: 177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu -J591)<br>* Eligible patients will receive a single dose of 177Lu-J591 (65 or 70 mCi/m2) consisting of J591 chelated at a specific activity of 12-15 mCi of 177Lu per mg of antibody plus sufficient non-radiolabeled, non-DOTA-conjugated (naked) J591 to achieve a total antibody dose of 20 mg. Each dose will be administered by an IV infusion at a rate not to exceed 5 mg/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the PSA Response Rate. | PSA response rate corresponds to change form baseline in PSA at any of the time points specified. | At baseline, Day 1, 29, 43, 57, 85, week 18, week 24 & every 12 weeks | 
| Define the Measurable Disease Response Rate. | Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study | Disease will be assessed at baseline and day 85. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the Duration of Biochemical PSA and/or Measurable Disease Response. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, Complete Response (CR) = Disappearance of all target lesions, Partial Response (PR) = A </=30% decrease in the sum of the longest diameter of target lesions, taking as reference the Baseline sum longest diameter, Stable Disease (SD) = Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started, Progressive Disease (PD) = A >/=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one or more new lesions | At baseline, and up to death | 
| Define the Toxicity of 177Lu-J591 Given as Single Dose. | Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL*. Grade 3 Severe or medically significant but not immediately life-threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | From baseline until end of treatment phase (12 weeks) | 
| Define the Incidence of Human Anti-J591 Antibody (HAHA) Response. |  | HAHA samples will be drawn at baseline and Day 85. | 
| Number of Participants With Hematological Toxicity Relative to Bone Marrow Involvement (Bone Scan Index). | Bone scan score determined for each patient and related to the degree of hematological toxicity quantified by % decline of nadir platelet count relative to baseline count. | Bone scan will be performed at baseline and Day 85. | 
| Assess the Survival Rate of Patients Following Treatment. |  | From baseline through study completion | 
| Number of Participants With Targeting of 177Lu-J591 to Known Tumor Sites. |  | Scans will be performed between day 6 and 8. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer