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

NCT ID: NCT00859781

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2026-05-31

Brief Summary

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.

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).

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1. 177Lu-J591 + Ketoconazole

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

Group Type: EXPERIMENTAL

177Lu-J591

Intervention Type: DRUG

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

Ketoconazole

Intervention Type: DRUG

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)

Hydrocortisone

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Ketoconazole

Intervention Type: DRUG

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)

Hydrocortisone

Intervention Type: DRUG

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

111In-J591

Intervention Type: DRUG

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

Interventions

177Lu-J591

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

Intervention Type: 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)

Intervention Type: DRUG

Hydrocortisone

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

Intervention Type: DRUG

111In-J591

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

Intervention Type: DRUG

Other Intervention Names

J591; Nizoral; Cortef; J591

Eligibility 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 (see Appendix C)
• Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®, Quadramet®)
• Platelet count <150,000/mm3 or known primary qualitative platelet disorder
• Absolute neutrophil count (ANC) <2,000/mm3
• Hematocrit <30 percent and Hemoglobin < 10 g/dL
• Abnormal coagulation profile (PT or INR, PTT > 1.3x ULN) unless on therapeutic anticoagulation - see concomitant meds section
• Serum creatinine >2.5 mg/dL
• AST (SGOT) >2x ULN
• Bilirubin (total) >1.5x ULN; subjects with Gilbert's syndrome will be allowed if direct bilirubin is within institutional normal limits
• Active serious infection
• Active angina pectoris or NY Heart Association Class III-IV
• ECOG Performance Status > 2
• Life expectancy <12 months
• History of deep vein thrombosis and/or pulmonary embolus within 1 month 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 4 weeks of treatment. Furthermore, other investigational therapy is not permitted during the treatment phase.
• Prior use of ketoconazole for the purposes of prostate cancer therapy for greater than 1 month
• Known history of HIV. The effects of J591 are unknown in this population. Furthermore, ketoconazole has many well-described drug-drug interactions which could affect antiviral therapy. If necessary, this population will be studied separately.
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.

• Known history of known myelodysplastic syndrome
• Adrenal hormone inhibitors (other than ketoconazole) within 4 weeks prior to study enrollment
• Finasteride (Propecia® or Proscar®) or dutasteride (Avodart®) within 4 weeks of enrollment
• Patients on corticosteroids prior to enrollment must have either discontinued and shown biochemical progression or have biochemical progression on a stable dose

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott T Tagawa, M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Cedars Sinai

Los Angeles, California, United States

USC/Norris Comprehensive cancer center

Los Angeles, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

The University of Kansas Cancer Center

Westwood, Kansas, United States

Weill Cornell Medical College

New York, New York, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

J591+Ketoconazole

Identifier Type: OTHER

Identifier Source: secondary_id

0810010067

Identifier Type: -

Identifier Source: org_study_id