Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

MLN2704 in Treating Patients With Progressive Metastatic Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03097 MILLENNIUM-M59102-051, NCT00070837

Objectives

Primary

1. Determine the dose-limiting toxicity and maximum tolerated dose of MLN2704 (administered in two different dosing schedules) in patients with progressive metastatic androgen-independent prostate cancer.

Secondary

1. Determine the pharmacokinetics of this drug in these patients.
2. Determine the anti-MLN591 antibody and anti-MLN2704 antibody response in patients treated with this drug.
3. Determine the disease response in patients treated with this drug, through changes in either prostate-specific antigen levels or anatomically measurable disease.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed prostate adenocarcinoma
  • Metastatic disease by radiography



• Progressive disease*, defined by the presence of at least 1 of the following despite castrate levels of testosterone (less than 50 ng/dL):
  • 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 prostate-specific antigen (PSA) levels
    • PSA at least 5 ng/mL

   [Note: *If previously treated with antiandrogen therapy (e.g., flutamide, bicalutamide, or nilutamide), disease progression must be demonstrated after discontinuation of antiandrogen therapy]




• Must remain on luteinizing hormone-releasing hormone analog therapy during study treatment unless surgically castrate



• No history of CNS metastasis, including incompletely treated epidural disease

Prior/Concurrent Therapy:

Biologic therapy

• No prior or concurrent monoclonal antibody therapy, including Prostascint®
• No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or other white blood cell colony-stimulating factors, in the absence of febrile neutropenia
• No concurrent medication to support platelet count (e.g., interleukin-11 [ Neumega®])

Chemotherapy

• More than 6 weeks since prior cytotoxic chemotherapy
• No concurrent cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 6 weeks since prior antiandrogen therapy
• More than 4 weeks since prior corticosteroids and/or adrenal hormone inhibitors
• No concurrent corticosteroids and/or adrenal hormone inhibitors
• No concurrent antiandrogen therapy
• No concurrent finasteride

Radiotherapy

• More than 6 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior PC-SPES
• No concurrent PC-SPES
• No concurrent aspirin and/or nonsteroidal anti-inflammatory agents when platelet count is less than 50,000/mm³

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hematocrit at least 27%
• No other serious illness involving the hematologic system that would preclude study participation

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST or ALT no greater than 1.5 times ULN
• PT normal
• INR normal
• PTT normal
• No history of hepatitis B or C
• No other serious illness involving the hepatic system that would preclude study participation

Renal

• Creatinine no greater than 2.0 mg/dL

  OR

• Creatinine clearance at least 60 mL/min
• Calcium no greater than 12.5 mg/dL
• No other serious illness involving the renal system that would preclude study participation

Cardiovascular

• No history of stroke
• No active angina pectoris
• No New York Heart Association class III or IV heart disease
• No other serious illness involving the cardiac system that would preclude study participation

Pulmonary

• No other serious illness involving the respiratory system that would preclude study participation

Other

• Fertile patients must use effective barrier contraception
• HIV negative
• No grade 2 or greater peripheral neuropathy
• No history of seizure disorder requiring active treatment
• No active serious infection not controlled by antibiotics
• No other serious illness involving the CNS system that would preclude study participation

Expected Enrollment

Approximately 46 patients (23 per dosing schedule) will be accrued for this study within 8 months.

Outcomes

Prostate-specific antigen (PSA) serum levels as assessed by PSA Working Group criteria

Disease progression as measured by clinical evaluation and/or radiographic studies
Anatomically measurable disease response as assessed by RECIST criteria within 4 weeks after complete or partial response
Safety

Outline

This is an open-label, dose-escalation, multicenter study. Patients are assigned to 1 of 2 dosing schedules.

• Phase I:
  • Schedule 1: Patients receive MLN2704 IV once every 2 weeks for 12 weeks (6 total doses) in the absence of disease progression or unacceptable toxicity. After receiving 6 doses, patients with at least a 50% decline in prostate-specific antigen (PSA) levels or a partial response (PR) or complete response (CR) may receive an additional 6 weeks of therapy (3 additional doses).
  
  
  
  • Schedule 2: Patients receive MLN2704 IV once a week for 12 weeks (12 total doses) in the absence of disease progression or unacceptable toxicity. After receiving 12 doses, patients with at least a 50% decline in PSA levels or a PR or CR may receive an additional 6 weeks of therapy (6 additional doses).
  
  
  

  In both schedules, 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.




• Phase II: Once the MTD is determined, a total of 14 patients receive MLN2704 at the MTD as in phase I.

Patients are followed at 15 days, 30 days, and then every 3 months until disease progression.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Howard Scher, MD, Principal investigator		Ph: 646-422-4330; 800-525-2225 Email: scherh@mskcc.org

Registry Information
Official Title		A Phase I/II Dose Escalation Trial of Multiple Doses of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects with Metastatic Androgen-Independent Prostate Cancer
Registered in ClinicalTrials.gov		NCT00070837
Date Submitted to PDQ		2003-10-22
Information Last Verified		2006-01-18
NCI Grant/Contract Number		P30-CA08748

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