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

Condition(s) targeted: Prostate Cancer

Intervention: 177Lu-J591 (Drug); Ketoconazole (Drug); Hydrocortisone (Drug); 111In-J591 (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Weill Medical College of Cornell University

Official(s) and/or principal investigator(s):
Scott T Tagawa, M.D., Principal Investigator, Affiliation: Weill Medical College of Cornell University

Overall contact:
Gina Mileo, R.N., Phone: 212-746-5430, Email: gjm2003@med.cornell.edu

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome: PSA response rate

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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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.

Gina Mileo, R.N., Phone: 212-746-5430, Email: gjm2003@med.cornell.edu

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, United States; Recruiting
Becky Runkel, Phone: 317-278-0571, Email: rrunkel@iupui.edu
Noah Hahn, M.D., Principal 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., Sub-Investigator

University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States; Recruiting
Pamela Zehr, RN, MA, Phone: 319-353-8914, Email: pamela-zehr@uiowa.edu
Daniel Vaena, M.D., Principal Investigator
James Brown, M.D., Sub-Investigator
Michael Graham, M.D., Sub-Investigator

Weill Cornell Medical College, New York, New York 10021, United States; Recruiting
Gina Mileo, R.N., Phone: 212-746-5430, Email: gjm2003@med.cornell.edu
Scott T Tagawa, M.D., Principal Investigator
David M Nanus, M.D., Sub-Investigator

Starting date: June 2009
Last updated: November 4, 2010