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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Radiation: lutetium Lu 177 monoclonal antibody J591

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00081172

CDR0000360629 (Registry Identifier)

MSKCC-03144

Details and patient eligibility

About

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.

Full 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.

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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