177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With Prostate Cancer - Full Text View

Sponsor:	Weill Medical College of Cornell University
Information provided by:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00859781

Purpose

The purpose of this study is to test the effectiveness of the experimental drug, 177Lu-J591 in combination with ketoconazole and hydrocortisone against prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: 177Lu-J591 Drug: Ketoconazole Drug: Hydrocortisone Drug: 111In-J591	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer After Local Therapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Nuclear Scans Prostate Cancer

Drug Information available for: Hydrocortisone acetate Hydrocortisone Ketoconazole Proctofoam-HC Fungarest Hydrocortisone hemisuccinate Hydrocortamate Immunoglobulins Hydrocortisone 21-sodium succinate Hydrocortisone cypionate Cortisol succinate Cortisol 21-phosphate Globulin, Immune

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

Proportion free of radiographically evident metastases at 18 months by CT and/or MRI scan of the abdomen and pelvis, chest x-ray or CT scan of the chest and bone scan [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

PSA response rate [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	June 2009
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1. 177Lu-J591+Ketoconzole Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 177Lu-J591 Infusion, continue ketoconazole and hydrocortisone	Drug: 177Lu-J591 177Lu-J591 70 mCi/m2 on day 29 (+/- 2 days) of treatment Drug: Ketoconazole Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg) Other Name: Nizoral Drug: Hydrocortisone Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg) Other Name: Cortef
Placebo Comparator: 2. 111In-J591 + ketoconazole Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 111In-J591 (placebo) Infusion, continue ketoconazole and hydrocortisone	Drug: Ketoconazole Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg) Other Name: Nizoral Drug: Hydrocortisone Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg) Other Name: Cortef Drug: 111In-J591 111In-J591 at a dose of 5 mCi on day 29 (+/- 2 days) of treatment

Arms

Assigned Interventions

Experimental: 1. 177Lu-J591+Ketoconzole

Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 177Lu-J591 Infusion, continue ketoconazole and hydrocortisone

Drug: 177Lu-J591

177Lu-J591 70 mCi/m2 on day 29 (+/- 2 days) of treatment

Drug: Ketoconazole

Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg)

Other Name: Nizoral

Drug: Hydrocortisone

Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg)

Other Name: Cortef

Placebo Comparator: 2. 111In-J591 + ketoconazole

Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 111In-J591 (placebo) Infusion, continue ketoconazole and hydrocortisone

Drug: Ketoconazole

Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg)

Other Name: Nizoral

Drug: Hydrocortisone

Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg)

Other Name: Cortef

Drug: 111In-J591

111In-J591 at a dose of 5 mCi on day 29 (+/- 2 days) of treatment

Detailed Description:

This research is being done because the standard treatments for prostate cancer that has returned (PSA is elevated) after surgery and/or radiation and progressed on initial hormonal therapy are not curative. Existing treatments, such as the ketoconazole used as part of this study may decrease PSA temporarily, but unfortunately the cancer continues to grow. This experimental drug is designed to seek out all of the prostate cancer cells and to deliver a lethal dose of radiation to the areas of cancer, but not to normal areas. Some of the normal organs (liver, kidney and bone marrow) do receive some radiation dose that is within the acceptable limits.

The experimental drug in this study includes an antibody (abbreviated: mAb) called "J591". It is a protein molecule which can bind to a specific site on a prostate cancer cell. A very energetic radioactive (an unstable atom) metal called 177Lutetium (abbreviated: 177Lu) is attached to the J591 antibody. The fully assembled drug is called "177Lu-J591". The study will assess the potential of the energy given off by the radioactive compound to kill cancer cell. This study may also involve the use of 111Indium (abbreviated 111In). This is also an energetic radioactive particle, but does not generally give off enough energy to kill cancer cells, but allows researchers to take pictures. This radioactive particle is also attached to the J591 antibody (called 111In-J591) and will serve as a placebo (treatment with no active medicine).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate previously treated with surgery and/or radiotherapy.
Biochemical progression (rising PSA) after medical or surgical castration
High risk of systemic progression defined as:
1. Rising PSA as defined above and either:
2. Absolute PSA > 20 ng/mL AND/OR
3. PSA doubling time < 8 months
No evidence of local recurrence or distant metastases
Age >18 years.
Serum testosterone < 50 ng/ml
Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial.
Subjects on bisphosphonate therapy must be on a stable dose and must have started therapy > 4 weeks prior to protocol therapy.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Use of red blood cell or platelet transfusions within 4 weeks of treatment
Use of hematopoietic growth factors within 4 weeks of treatment
Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment
Prior radiation therapy encompassing >25% of skeleton
Prior treatment with 89-Strontium or 153-Samarium containing compounds (e.g. Metastron®, Quadramet®)
Platelet count <150,000/mm3
Absolute neutrophil count (ANC) <2,000/mm3
Hematocrit <30 percent or Hemoglobin < 10 g/dL
Abnormal coagulation profile (PT or INR, PTT) > 1.3x ULN
Serum creatinine >2.5 mg/dL
AST (SGOT) >2x ULN
Bilirubin (total) >1.5x ULN
Serum calcium >11 mg/dL
Active serious infection
Active angina pectoris or NY Heart Association Class III-IV
Karnofsky Performance Status <70
Life expectancy <12 months
History of deep vein thrombosis and/or pulmonary embolus within 3 months of study entry
Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
Prior investigational therapy (medications or devices) within 6 weeks of treatment.
Prior use of ketoconazole for the purposes of prostate cancer therapy
Known history of HIV.
Currently active other malignancy other than non-melanoma skin cancer.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00859781

Contacts

Contact: Gina Mileo, R.N.

212-746-5430

gjm2003@med.cornell.edu

Locations

United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Becky Runkel 317-278-0571 rrunkel@iupui.edu
Principal Investigator: Noah Hahn, M.D.
Sub-Investigator: Steven Beck, M.D.
Sub-Investigator: Richard Butler, M.D.
Sub-Investigator: Richard Foster, M.D.
Sub-Investigator: Thomas Gardner, M.D.
Sub-Investigator: Michael Koch, M.D.
Sub-Investigator: Theodore Logan, M.D.
Sub-Investigator: Chandru Sundaram, M.D.
Sub-Investigator: James Fletcher, M.D.
Sub-Investigator: Mark Tann, M.D.
United States, Iowa
University of Iowa Hospitals and Clinics	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Pamela Zehr, RN, MA 319-353-8914 pamela-zehr@uiowa.edu
Principal Investigator: Daniel Vaena, M.D.
Sub-Investigator: James Brown, M.D.
Sub-Investigator: Michael Graham, M.D.
United States, New York
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10021
Contact: Gina Mileo, R.N. 212-746-5430 gjm2003@med.cornell.edu
Principal Investigator: Scott T Tagawa, M.D.
Sub-Investigator: David M Nanus, M.D.

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Principal Investigator:

Scott T Tagawa, M.D.

Weill Medical College of Cornell University

More Information

No publications provided

Responsible Party:	Scott Tagawa, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00859781 History of Changes
Other Study ID Numbers:	0810010067, J591+Ketoconazole
Study First Received:	March 10, 2009
Last Updated:	November 4, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:

Prostate

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Antibodies, Monoclonal
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone

Ketoconazole
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 09, 2012