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
Overview
- Phase
- Phase 2
- Intervention
- 177Lu-J591
- Conditions
- Prostate Cancer
- Sponsor
- Weill Medical College of Cornell University
- Enrollment
- 55
- Locations
- 9
- Primary Endpoint
- Proportion of Participants Free of Radiographically Evident Metastases From Baseline to 18 Months After Study Drug Administration
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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).
Investigators
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:
- •Rising PSA as defined above and either:
- •Absolute PSA \> 20 ng/mL AND/OR
- •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.
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
Arms & Interventions
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
Intervention: 177Lu-J591
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
Intervention: Ketoconazole
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
Intervention: Hydrocortisone
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
Intervention: Ketoconazole
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
Intervention: Hydrocortisone
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
Intervention: 111In-J591
Outcomes
Primary Outcomes
Proportion of Participants Free of Radiographically Evident Metastases From Baseline to 18 Months After Study Drug Administration
Time Frame: Baseline and 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.
Secondary Outcomes
- Change in PSA Response Rate(Collected at screening, V2, V3, V5, V9 then every 4 weeks till PSA progression or end of study at approximately 100 months)