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Radioimmunotherapy in Prostate Cancer Using 177Lu-J591 Antibody

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00538668
First received: October 2, 2007
Last updated: February 1, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
Prostate Cancer Drug: 117Lu-J591 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Radioimmunotherapy Phase I Dose-Escalation Studies in Prostate Cancer Using 177Lu-J591 Antibody: Dose Fractionation Regimen

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Define the PK and dosimetry of 177Lu-J591 [ Time Frame: Perform imaging and pharmacokinetic (PK) sampling during the first two weeks of treatment. ]
  • 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. ]
  • Determine the myelotoxicity of fractionated dose of 177Lu-J591 [ Time Frame: Lab tests will be performed weekly. ]
  • 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 Measures:
  • 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. ]
  • 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 ]

Enrollment: 54
Actual Study Start Date: August 2007
Estimated Study Completion Date: December 2018
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
20 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 2
25 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 3
30 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 4
35 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 5
40 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 6
45 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 7
50 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 8
55 mCi/m2 of 177Lu-J591 will be given in 2 doses, 2 weeks apart.
Drug: 117Lu-J591
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.
Experimental: 9
25 mCi/m2 of 177Lu-J591 will be given every 2 weeks.
Drug: 117Lu-J591
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.

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.

  Eligibility

Ages Eligible for Study:   21 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologic diagnosis (recent or remote) of prostate adenocarcinoma.
  2. 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 osseous lesions on bone scan and/or
    • rising PSA
  3. Rising PSA on 3 serial determinations over a period of ≥ 2 weeks.
  4. If patient is being treated with an LHRH analog, the drug:

    • must be maintained for the duration of this study or
    • must be terminated ≥ 10 weeks prior to entry (for 28 day depot preparations) or 24 weeks (for 3 month depot preparations) or 32 weeks (for 4 month depot preparation).
  5. Platelet count > 150,000/mm3.
  6. Absolute neutrophil count (ANC) ≥ 2,000/mm3
  7. Normal coagulation profile (PT, PTT), unless on a stable anticoagulation regimen
  8. Hematocrit > 30% or Hemoglobin > 10g/dL without blood transfusion dependency
  9. Patients of child bearing potential must agree to use an effective method of contraception.
  10. Patient must have progressed following discontinuation of anti-androgen therapy, if received.
  11. Serum testosterone < 50 ng/ml.

Exclusion Criteria:

  1. Prior aspirin and/or non-steroidal anti-inflammatory agents within 1 week of study treatment.
  2. Prior corticosteroids and/or adrenal hormone inhibitors within 4 weeks of treatment, except for low dose maintenance prednisone or hydrocortisone (i.e. for adrenal insufficiency) on a stable dose at the investigator's discretion.
  3. Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment.
  4. Prior radiation therapy encompassing >25% of expected red marrow distribution.
  5. Prior treatment with 89Strontium (Metastron®) or 153Samarium (Quadramet®). CNS metastasis.
  6. History of seizure and/or stroke within past 2 years
  7. History of HIV
  8. Serum creatinine > 2.0
  9. SGOT > 2x ULN
  10. Bilirubin (total) >1.5x ULN
  11. Serum calcium > 12.5
  12. Active infection
  13. Active angina pectoris or NY Heart Association Class III-IV.
  14. Karnofsky Performance Status < 60; ECOG Performance Status > 2.
  15. Life expectancy < 6 months
  16. 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.
  17. Prior treatment with monoclonal Ab J591 labeled with therapeutic doses of 177Lu or 90Y
  18. Other investigational therapy within 4 weeks of treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538668

Locations
United States, New York
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Scott Tagawa, M.D. Weill Medical College of Cornell University
  More Information

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00538668     History of Changes
Other Study ID Numbers: 0602008378
Repetitive dosing 177Lu-J591
Study First Received: October 2, 2007
Last Updated: February 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Weill Medical College of Cornell University:
Prostate
Prostate Cancer
Prostate Ca

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2017