MLN2704 in Treating Patients With Progressive Metastatic Prostate Cancer

RATIONALE: Monoclonal antibodies such as MLN2704 can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effect of MLN2704 on the body in treating patients who have progressive metastatic prostate cancer.

OBJECTIVES:

• Determine the dose-limiting toxicity and maximum tolerated dose of MLN2704 immunoconjugate in patients with progressive metastatic androgen-independent prostate cancer.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the prostate-specific antigen and disease response in patients treated with this drug.
• Determine the anti-MLN591 antibody and anti-MLN2704 antibody response to this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive MLN2704 IV over 2.5 hours on day 1. Treatment repeats every 6-8 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients with responsive disease after 3 doses of therapy may receive additional therapy as above at the investigator's discretion.

Cohorts of 3-6 patients receive escalating doses of MLN2704 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate adenocarcinoma

  • Metastatic disease

• Progressive disease by physical exam, imaging studies, and/or rising prostate-specific antigen (PSA) levels defined by at least 1 of the following criteria*:

  • Progressive tumor lesions (changes in the size of lymph nodes or parenchymal masses on physical exam or x-ray and CT scan or MRI)
  • Progressive bone metastases (presence of new lesion[s] on a bone scan)

  • Progressive PSA levels despite castrate levels of testosterone

    • PSA at least 5 ng/mL
  • Progression of disease demonstrated after completion of antiandrogen therapy NOTE: *Patients whose sole manifestation of progressive disease is an increase in disease-related symptoms are not eligible
• Measurable or evaluable disease
• Failed prior hormonal therapy (including antiandrogen withdrawal therapy)
• No history of CNS metastasis (including epidural disease)

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hematocrit greater than 30%
• No serious hematologic illness that would preclude study completion or interfere with determination of causality of study adverse events

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST or ALT no greater than 1.5 times ULN
• PTT normal
• PT and INR normal
• No serious hepatic illness that would preclude study completion or interfere with determination of causality of study adverse events

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 60 mL/min
• Calcium less than 12.5 mg/dL
• No serious renal illness that would preclude study completion or interfere with determination of causality of study adverse events

Cardiovascular

• No history of stroke
• No active angina pectoris
• No New York Heart Association class III or IV heart disease
• No serious cardiac illness that would preclude study completion or interfere with determination of causality of study adverse events

Pulmonary

• No serious respiratory illness that would preclude study completion or interfere with determination of causality of study adverse events

Other

• Fertile patients must use effective barrier contraception
• HIV negative
• No history of seizure disorder requiring active treatment
• No serious CNS illness that would preclude study completion or interfere with determination of causality of study adverse events
• No grade 2 or greater peripheral neuropathy
• No active serious infection not controlled by antibiotics
• No other serious illness that would preclude study completion or interfere with determination of causality of study adverse events

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior monoclonal antibody therapy (including Prostacint®)
• No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or other white cell colony-stimulating factors, except for febrile neutropenia
• No concurrent interleukin-11 for platelet count support

Chemotherapy

• More than 6 weeks since prior cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 4 weeks since prior corticosteroids and/or adrenal hormone inhibitors
• More than 6 weeks since prior antiandrogen therapy (e.g., flutamide, bicalutamide, or nilutamide)
• No prior finasteride (Proscar® or Propecia®)

• Luteinizing hormone-releasing hormone (LHRH) analog therapy allowed if 1 of the following circumstances exists:

  • If patient is currently receiving LHRH analog therapy, therapy must be maintained for study duration
  • If patient discontinued LHRH analog therapy prior to study entry, therapy must be discontinued at least 10 weeks prior to study entry for 1-month depot preparations, 24 weeks for 3-month depot preparations, or 32 weeks for 4-month depot preparations

Radiotherapy

• More than 6 weeks since prior radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior PC-SPES
• No other concurrent medication for platelet count support