Radiolabeled Monoclonal Antibody in Treating Patients With Progressive Metastatic Androgen-Independent Adenocarcinoma (Cancer) of the Prostate

A Phase II Trial Of Lu Radiolabeled Monoclonal Antibody HuJ591-GS (Lu-J591) In Patients With Metastatic Androgen-Independent Prostate Cancer

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying how well radiolabeled monoclonal antibody works in treating patients with progressive metastatic androgen-independent adenocarcinoma (cancer) of the prostate.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: lutetium Lu 177 monoclonal antibody J591

Detailed Description

OBJECTIVES:

Primary

• Determine the prostate-specific antigen (PSA) response rate in patients with progressive metastatic androgen-independent adenocarcinoma of the prostate treated with lutetium Lu 177 monoclonal antibody J591.
• Determine the measurable disease response rate in patients treated with this drug.

Secondary

• Determine the toxicity of this drug in these patients.
• Determine the duration of biochemical PSA and/or measurable disease response in patients treated with this drug.
• Determine the incidence of human anti-J591 antibody (HAHA) response in patients treated with this drug.
• Correlate hematological toxicity of this drug with bone marrow involvement (bone scan index) in these patients.
• Determine the survival rate in patients treated with this drug.
• Determine the targeting of this drug to known tumor sites in these patients.
• Determine the tumor-absorbed radiation dose in patients treated with this drug.

OUTLINE: This is a multicenter, open-label study.

Patients receive a single dose of lutetium Lu 177 monoclonal antibody J591 IV on day 1. Patients then undergo radionuclide scanning between days 6-8 to confirm tumor targeting by the study drug.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 17-32 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Metastatic disease

• Progressive disease after prior antiandrogen therapy, as evidenced by at least 1 of the following parameters:

  • New osseous lesions on bone scan
  • Greater than 25% increase in the sum of the products of the longest perpendicular diameters of the lesions OR the appearance of new lesions on MRI or CT scan

  • Rising prostate-specific antigen (PSA) despite adequate medical or surgical castration therapy

    • Consecutive increase in PSA, determined by two separate measurements taken at least 1 week apart and confirmed by a third, and if necessary, a fourth measurement
    • PSA must be ≥ 5 ng/mL and ≥ 25% above the previous nadir
• Measurable or evaluable disease
• Serum testosterone ≤ 50 ng/dL
• No confluent lesions involving axial and appendicular skeleton on bone scan ("superscan")

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm^3
• Hematocrit ≥ 30%
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 150,000/mm^3
• No serious hematologic illness that would preclude study participation

Hepatic

• AST ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• PTT normal
• PT normal OR
• INR normal
• No serious hepatic illness that would preclude study participation

Renal

• Creatinine ≤ 2.5 mg/dL
• Calcium ≤ 11 mg/dL
• No serious renal illness that would preclude study participation

Cardiovascular

• No New York Heart Association class III or IV heart disease
• No active angina pectoris
• No prior deep vein thrombophlebitis within the past 3 months
• No other serious cardiac illness that would preclude study participation

Pulmonary

• No pulmonary embolus within the past 3 months
• No other serious respiratory illness that would preclude study participation

Other

• Fertile patients must use effective contraception
• HIV negative
• No serious CNS illness that would preclude study participation
• No active serious infection not controlled by antibiotics
• No other serious illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior red blood cell or platelet transfusions
• More than 2 weeks since prior hematopoietic growth factors
• No prior monoclonal antibody therapy except ProstaScint®
• No other concurrent monoclonal antibody-based therapy
• No concurrent medication to support platelet count (e.g., oprelvekin)

Chemotherapy

• More than 4 weeks since prior cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics

• Concurrent luteinizing hormone-releasing hormone (LHRH) analog allowed provided 1 of the following is true:

  • Treatment is maintained during study participation
  • Treatment is terminated at least 10 weeks (for 1-month depot preparations), 24 weeks (for 3-month depot preparations), or 32 weeks (for 4-month depot preparations) prior to study entry
• More than 4 weeks since prior corticosteroids
• More than 4 weeks since prior adrenal hormone inhibitors
• Concurrent low-dose prednisone (≤ 5mg/day) for adrenal insufficiency allowed
• No concurrent finasteride

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of skeleton
• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium-containing compounds (e.g., Metastron® or Quadramet®)

Surgery

• Not specified

Other

• More than 4 weeks since prior PC-SPES
• More than 4 weeks since prior investigational therapy (medications or devices)
• At least 1 week since prior aspirin and/or nonsteroidal anti-inflammatory agents possessing antiplatelet activity

• At least 1 week since prior antiplatelet medication, including the following:

  • Abciximab
  • Cilostazol
  • Clopidogrel
  • Dipyridamole
  • Ticlopidine

• No concurrent anticoagulant medications (for platelet count < 50,000/mm^3), including the following:

  • Dalteparin
  • Danaparoid
  • Enoxaparin
  • Heparin
  • Warfarin
• No other concurrent investigational therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Biochemical response as measured by prostate-specific antigen level at 8 weeks after treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Study Completion (ACTUAL): May 1, 2006

Study Registration Dates

• First Submitted: April 7, 2004
• First Submitted That Met QC Criteria: April 7, 2004
• First Posted (ESTIMATE): April 8, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: April 1, 2006

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: MSKCC-03144; CDR0000360629 (REGISTRY: PDQ (Physician Data Query))