Pilot Trial of Chemohormonal Therapy Followed by Prostatectomy in High Risk Prostate Cancer

Per a protocol amendment approved on 9/5/2019 - two ferumoxytol MRI scans were added for 3 participants, represented here as an additional arm.

Inclusion criteria

• Histologically confirmed adenocarcinoma of the prostate without signet cell or small cell features.
• High risk prostate cancer defined as extracapsular extension (cT3a) or seminal vesicle involvement (cT3b) or invasion of adjacent structures (cT4), serum PSA greater than 20 ng/mL or Gleason score of 8 to 10 and/or regional lymph node or
• Oligometastatic disease defined as disseminated metastases beyond regional lymph nodes that meet the following criteria:

• No visceral metastases
• Less than four bony metastases.
• Ability to comply with all study procedures and willingness to remain supine for 120 minutes during imaging.
• Patients must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
• Patients must be considered candidates for prostatectomy as per standard of care.
• Adequate hematologic and renal function as evidenced by the following within 4 weeks of day 1:

• ANC greater than or equal to 1500/mm3
• Hemoglobin (HgB) greater than or equal to 10.0 gr/dL independent of transfusion
• Platelets greater than or equal to 100,000/mm3
• Creatinine less than or equal to 2.0 mg/dL
• Total bilirubin less than or equal to Upper Limit of Normal (ULN)
• Estimated life expectancy of greater than or equal to 12 months at screening.
• Throughout the study, patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) from screening through 3 months after last dose of study drug. Two acceptable methods of birth control thus include the following:

• A condom (barrier method of contraception) AND One of the following is required:
• Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner
• Placement of an intrauterine device or intrauterine system by the female partner
• Additional barrier method: Contraceptive sponge or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner
• Tubal ligation in the female partner performed at least 6 months before screening
• Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), performed at least 6 months before screening
• While receiving chemotherapy, the patient must use a condom if having sex with a pregnant woman.
• Must agree not to donate sperm from first dose of study drug through 3 months after the last dose of study drug.

Exclusion criteria

• Prior treatment for prostate cancer, including ADT, orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide.
• Prior radiation to the prostate.
• Use of other investigational agent for prostate cancer.
• No active secondary malignancy
• Chronic liver disease or abnormal liver function:

• Total bilirubin greater than ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is greater than ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) or
• Alanine (ALT) or aspartate (AST) aminotransferase greater than 2.0 x ULN or
• ALT or aspartate AST greater than 1.5 x ULN concomitant with alkaline phosphatase greater than 2.5 x ULN.
• Peripheral neuropathy grade greater than 1.
• Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within the previous 6 months.
• Major surgery within 4 weeks before screening.
• Patients with known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol.
• Herbal supplements that have been shown to modulate testosterone or androgen signaling (e.g. Saw Palmetto) are not allowed while on study.
• Subjects may not be enrolled concurrently on other treatment studies. Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial; places the patient at undue risk; or complicates the interpretation of the data, in the opinion of the investigator or medical monitor.
• Subjects who will be receiving Ferumoxytol MRI tracer must:

• Not have any known hypersensitivity to Feraheme or any of its components
• Must not have a history of allergic reaction to any intravenous iron product.
• Must not have a known iron overload (based on medical history)