A Phase I Single Ascending Dose Trial of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen Independent Prostate Cancer
Inclusion Criteria
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