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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00859781
• Other study ID #: 0810010067
• Secondary ID: J591+Ketoconazol
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2009
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: December 2025
• Est. primary completion date: February 10, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 177Lu-J591
177Lu-J591 70 mCi/m2 on day 29 (+/- 2 days) of treatment
• 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)
• Hydrocortisone
Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg)
• 111In-J591
111In-J591 at a dose of 5 mCi on day 29 (+/- 2 days) of treatment

Locations

Country	Name	City	State
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	Cedars Sinai	Los Angeles	California
United States	USC/Norris Comprehensive cancer center	Los Angeles	California
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	Georgetown University Medical Center	Washington	District of Columbia
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Free of Radiographically Evident Metastases From Baseline to 18 Months After Study Drug Administration	Subjects will perform a CT and/or MRI scan of the abdomen and pelvis, chest x-ray or CT scan of the chest and bone scan to determine the proportion of participants free of radiographically evident metastases from baseline to 18 months after study drug administration.	Baseline and 18 months after study drug administration
Secondary	Change in PSA Response Rate	PSA response will be determined by comparing the PSA levels after therapy to the baseline and pre-treatment PSA via blood specimens	Collected at screening, V2, V3, V5, V9 then every 4 weeks till PSA progression or end of study at approximately 100 months