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Radioimmunotherapy in Prostate Cancer Using 177Lu-J591 Antibody

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
117Lu-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, Prostate Cancer, Prostate Ca

Eligibility Criteria

21 Years - 85 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria

  • Histologic diagnosis (recent or remote) of prostate adenocarcinoma

  • Progressive, castrate metastatic carcinoma of the prostate defined by presence of metastatic disease on imaging and:

    • progressive tumor lesions on CT or MRI and/or
    • new osseus lesions on bone scan and/or

    • rising PSA

      • Rising PSA on 3 serial determinations over a period of greater than 2 weeks. An increase in PSA must be determined by two separate measurements taken at least one week apart and confirmed by a third and if necessary, a fourth measurement. If the third measurement is not greater than the second, then a fourth measurement must be taken. The fourth measurement must be greater than the second measurement for the patients to be eligible for enrollment in the study. The minimum final PSA must be > 2.
  • For subjects who have not undergone surgical orchiectomy, LHRH agonist or antagonist therapy must me maintained for the duration of this study
  • Platelet count > 150,000/mm3
  • Absolute neutrophil count (ANC) ≥ 2,000/mm3
  • Normal coagulation profile (defined as PT or INR and PTT < 1.3x ULN), unless on a stable anticoagulation regimen
  • Hematocrit > 27% or Hemoglobin > 9 g/dL without blood transfusion dependency
  • Patients of child bearing potential must agree to use an effective method of contraception
  • Patient must have progressed following discontinuation of anti-androgen therapy, if received
  • Serum testosterone < 50 ng/ml

Exclusion Criteria

  • Prior corticosteroids and/or adrenal hormone inhibitors within 4 weeks of treatment, except for low dose maintenance prednisone or hydrocortisone (i.e. for adrenal insufficienty) on a stable dose at the investigator's discretion
  • Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment.
  • Prior radiation therapy encompassing >25% of expected red marrow distribution.
  • Prior treatment with 89Strontium (Metastron®) or 153Samarium (Quadramet®)
  • CNS metastasis
  • History of seizure and/or stroke within past 6 months
  • Known history of HIV
  • Serum creatinine > 2x ULN
  • AST > 2x ULN
  • Bilirubin (total) > 1.5x ULN; subjects with Gilbert's syndrome will be allowed if direct bilirubin is within institutional normal limits
  • Serious active infection (as assessed by investigator)
  • Active angina pectoris or NY Heart Association Class III-IV
  • ECOG Performance Status > 2
  • Life expectancy < 6 months
  • Age < 21 y.o
  • 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 treatment with monoclonal Ab J591 labeled with therapeutic doses of 177Lu or 90Y
  • Other investigational therapy within 4 weeks of treatment
  • Inability to understand and the willingness to sign a written informed consent document or to follow investigational procedures in the opinion of the investigator

Sites / Locations

  • Weill Cornell Medical College-New York Presbyterian Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

5

6

7

8

9

Arm Description

20 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

25 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

30 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

35 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

40 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

45 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

50 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

55 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.

25 mCi/m2 of 177Lu-J591 will be given every 2 weeks.

Outcomes

Primary Outcome Measures

Define the PK and dosimetry of 177Lu-J591
Determine the cumulative maximum tolerated dose of 177Lu-J591 in a 2 week dose-fractionation regimen.
Determine the myelotoxicity of fractionated dose of 177Lu-J591
Define the preliminary efficacy (response rate) of 177Lu-J591

Secondary Outcome Measures

Monitor biochemical (PSA) and/or measurable disease response and duration.
Estimate radiation dosimetry of 177Lu-J591 and correlate toxicity with radiation dosimetry.

Full Information

First Posted
October 2, 2007
Last Updated
March 16, 2021
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT00538668
Brief Title
Radioimmunotherapy in Prostate Cancer Using 177Lu-J591 Antibody
Official Title
Radioimmunotherapy Phase I Dose-Escalation Studies in Prostate Cancer Using 177Lu-J591 Antibody: Dose Fractionation Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
August 2007 (Actual)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
June 2020 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to test the safety of the experimental drug, 177Lu-J591 and see what effects (good and bad) it has on your prostate cancer. Another purpose is to find the highest dose of the drug that can be given without causing severe side effects.
Detailed Description
Study Design: We plan to perform a phase I dose-escalation study. The trial is designed to determine the cumulative MTD in a FDR in which 177Lu-J591 will be given in 2 doses, 2 weeks apart. The dose escalation will start at 20 mCi/m2 and escalate in increments of 5 mCi/m2 to 55 mCi/m2 in up to 8 cohorts.We plan to recruit a maximum of 68 subjects in this trial. Specific Aims: 1. Determine the cumulative MTD of 177Lu-J591 in a 2 week dose-fractionation regimen. 2. Perform imaging and pharmacokinetic (PK) studies with 177Lu-J591 in order to define the PK and dosimetry of 177Lu-J591 3. Determine the myelotoxicity of fractionated dose of 177Lu-J591 4. Monitor biochemical (PSA) and/or measurable disease response and duration. Following the administration of 177Lu-J591 mAb on day 0, blood samples may be obtained at 10 min, 1, 2, 4 hrs, days 1, once during days 3-6, day 7 and 14. In addition, total body images may be obtained on day 0 at 1-4 hours after study treatment, day 1, once during days 3-6, days 7 and 14 using a gamma camera. (Amendment dated 15 July 2009: As investigators have gained ample information from the initial cohorts, PK and 177Lu-J591 imaging studies (other than the day 6-8 scan) will be considered optional.) Patients will be followed for a minimum of 12 weeks after the 2nd dose of 177Lu-J591 (total 14 weeks) or until toxicities resolve, disease progression or administration of alternative therapy for the patient¿s prostate cancer. Various clinical and laboratory evaluations will be performed during the first week and then every week until 12 weeks. These include, blood chemistries, CBCs, serum PSA levels, etc. If the patient¿s disease is stable or responding at 12 weeks after his last dose, he will continue to be followed until progression of disease. During the long-term follow-up, the patient¿s PSA will be monitored at least every 6 weeks and CT/bone scans will be evaluated at least every 18 weeks until disease progression.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
20 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
2
Arm Type
Experimental
Arm Description
25 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
3
Arm Type
Experimental
Arm Description
30 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
4
Arm Type
Experimental
Arm Description
35 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
5
Arm Type
Experimental
Arm Description
40 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
6
Arm Type
Experimental
Arm Description
45 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
7
Arm Type
Experimental
Arm Description
50 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
8
Arm Type
Experimental
Arm Description
55 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Arm Title
9
Arm Type
Experimental
Arm Description
25 mCi/m2 of 177Lu-J591 will be given every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
117Lu-J591
Intervention Description
There will be 9 groups of patients. The first group will receive 20 units of test drug and the 9th group will receive 55 units of the test drug. The exact dose of the test drug will depend upon how many patients have been included in this protocol at the time of patient enrollment. Patients will receive 20-55 units (or millicuries) of radioactivity depending upon patient specific height and weight. The assignment of each patient for a specific dose level is purely based on the sequence of recruitment basis and does not depend on the clinical status of the patient.
Primary Outcome Measure Information:
Title
Define the PK and dosimetry of 177Lu-J591
Time Frame
Perform imaging and pharmacokinetic (PK) sampling during the first two weeks of treatment.
Title
Determine the cumulative maximum tolerated dose of 177Lu-J591 in a 2 week dose-fractionation regimen.
Time Frame
Will be determined baesd on toxicity experienced by patients at each dose level.
Title
Determine the myelotoxicity of fractionated dose of 177Lu-J591
Time Frame
Lab tests will be performed weekly.
Title
Define the preliminary efficacy (response rate) of 177Lu-J591
Time Frame
PSA will be evaluated at baseline and weeks 6, 10 and 14. Scan will be perfoemed at baseline and week 14.
Secondary Outcome Measure Information:
Title
Monitor biochemical (PSA) and/or measurable disease response and duration.
Time Frame
PSA will be evaluated at baseline and weeks 6, 10 and 14. Scan will be perfoemed at baseline and week 14.
Title
Estimate radiation dosimetry of 177Lu-J591 and correlate toxicity with radiation dosimetry.
Time Frame
Total body images will be obtained on day 0 at 1-4 hours after treatment, day 1, once during days 3-6, days 7 and 14

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Histologic diagnosis (recent or remote) of prostate adenocarcinoma Progressive, castrate metastatic carcinoma of the prostate defined by presence of metastatic disease on imaging and: progressive tumor lesions on CT or MRI and/or new osseus lesions on bone scan and/or rising PSA Rising PSA on 3 serial determinations over a period of greater than 2 weeks. An increase in PSA must be determined by two separate measurements taken at least one week apart and confirmed by a third and if necessary, a fourth measurement. If the third measurement is not greater than the second, then a fourth measurement must be taken. The fourth measurement must be greater than the second measurement for the patients to be eligible for enrollment in the study. The minimum final PSA must be > 2. For subjects who have not undergone surgical orchiectomy, LHRH agonist or antagonist therapy must me maintained for the duration of this study Platelet count > 150,000/mm3 Absolute neutrophil count (ANC) ≥ 2,000/mm3 Normal coagulation profile (defined as PT or INR and PTT < 1.3x ULN), unless on a stable anticoagulation regimen Hematocrit > 27% or Hemoglobin > 9 g/dL without blood transfusion dependency Patients of child bearing potential must agree to use an effective method of contraception Patient must have progressed following discontinuation of anti-androgen therapy, if received Serum testosterone < 50 ng/ml Exclusion Criteria Prior corticosteroids and/or adrenal hormone inhibitors within 4 weeks of treatment, except for low dose maintenance prednisone or hydrocortisone (i.e. for adrenal insufficienty) on a stable dose at the investigator's discretion Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment. Prior radiation therapy encompassing >25% of expected red marrow distribution. Prior treatment with 89Strontium (Metastron®) or 153Samarium (Quadramet®) CNS metastasis History of seizure and/or stroke within past 6 months Known history of HIV Serum creatinine > 2x ULN AST > 2x ULN Bilirubin (total) > 1.5x ULN; subjects with Gilbert's syndrome will be allowed if direct bilirubin is within institutional normal limits Serious active infection (as assessed by investigator) Active angina pectoris or NY Heart Association Class III-IV ECOG Performance Status > 2 Life expectancy < 6 months Age < 21 y.o 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 treatment with monoclonal Ab J591 labeled with therapeutic doses of 177Lu or 90Y Other investigational therapy within 4 weeks of treatment Inability to understand and the willingness to sign a written informed consent document or to follow investigational procedures in the opinion of the investigator
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 Cornell Medical College-New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36383907
Citation
Martiniova L, Zielinski RJ, Lin M, DePalatis L, Ravizzini GC. The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment. Cancer J. 2022 Nov-Dec 01;28(6):446-453. doi: 10.1097/PPO.0000000000000625.
Results Reference
derived
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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Radioimmunotherapy in Prostate Cancer Using 177Lu-J591 Antibody

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