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


Phase 1
N/A
N/A
Not Enrolling
Male
Prostate Cancer

Thank you

Trial Information

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

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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Howard I. Scher, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000288829

NCT ID:

NCT00058409

Start Date:

October 2002

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021