Clinical trial NCT00859781: 177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2009-03-11
Enrollment: 55
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Proportion of Participants Free of Radiographically Evident Metastases From Baseline to 18 Months After Study Drug Administration
timeFrame: Baseline and 18 months after study drug administration
Secondary outcomes:
measure: Change in PSA Response Rate
timeFrame: Collected at screening, V2, V3, V5, V9 then every 4 weeks till PSA progression or end of study at approximately 100 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive cancer center
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Weill Medical College of Cornell University
name: Scott T Tagawa, M.D.
role: PRINCIPAL_INVESTIGATOR
References: