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

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu -J591)
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate Cancer

Eligibility Criteria

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

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

Sites / Locations

  • Weill Medcial College of Cornell University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm Description

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.

Outcomes

Primary Outcome Measures

Define the PSA Response Rate.
PSA response rate corresponds to change form baseline in PSA at any of the time points specified.
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

Secondary Outcome Measures

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
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.
Define the Incidence of Human Anti-J591 Antibody (HAHA) Response.
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.
Assess the Survival Rate of Patients Following Treatment.
Number of Participants With Targeting of 177Lu-J591 to Known Tumor Sites.

Full Information

First Posted
September 14, 2005
Last Updated
September 6, 2017
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT00195039
Brief Title
Treatment With Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Prostate Cancer
Official Title
A Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Androgen-Independent Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 2004 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All patients
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu -J591)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Define the PSA Response Rate.
Description
PSA response rate corresponds to change form baseline in PSA at any of the time points specified.
Time Frame
At baseline, Day 1, 29, 43, 57, 85, week 18, week 24 & every 12 weeks
Title
Define the Measurable Disease Response Rate.
Description
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
Time Frame
Disease will be assessed at baseline and day 85.
Secondary Outcome Measure Information:
Title
Define the Duration of Biochemical PSA and/or Measurable Disease Response.
Description
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
Time Frame
At baseline, and up to death
Title
Define the Toxicity of 177Lu-J591 Given as Single Dose.
Description
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.
Time Frame
From baseline until end of treatment phase (12 weeks)
Title
Define the Incidence of Human Anti-J591 Antibody (HAHA) Response.
Time Frame
HAHA samples will be drawn at baseline and Day 85.
Title
Number of Participants With Hematological Toxicity Relative to Bone Marrow Involvement (Bone Scan Index).
Description
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.
Time Frame
Bone scan will be performed at baseline and Day 85.
Title
Assess the Survival Rate of Patients Following Treatment.
Time Frame
From baseline through study completion
Title
Number of Participants With Targeting of 177Lu-J591 to Known Tumor Sites.
Time Frame
Scans will be performed between day 6 and 8.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Tagawa, M.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Medcial College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
Citation
S.T. Tagawa; M.I. Milowsky; M. J. Morris; S. Vallabhajosula; S. Goldsmith; D. Matulich; J. Kaplan; F. Berger; H. I. Scher; N. H. Bander; D. M. Nanus. Phase II trial of 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 in patients with metastatic castrate-resistant prostate cancer. J Clin Oncol 26: 2008 (May 20 suppl; abstr 5140)
Results Reference
result
PubMed Identifier
23714732
Citation
Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, Osborne J, Goldsmith SJ, Larson S, Taskar NP, Scher HI, Bander NH, Nanus DM. Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013 Sep 15;19(18):5182-91. doi: 10.1158/1078-0432.CCR-13-0231. Epub 2013 May 28.
Results Reference
result
PubMed Identifier
33465252
Citation
Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.
Results Reference
derived

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

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