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

Study Overview
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Brief Summary
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This is a pilot multimodality treatment approach trial with androgen deprivation therapy in combination with docetaxel chemotherapy followed by radical prostatectomy in patients with newly diagnosed high-risk and oligometastatic prostate cancer. This study aims to evaluate the rates of complete pathologic response (pCR) at the time of prostatectomy as well as PSA response, time to PSA recurrence and safety and toxicity of the combination. This study will be heavily embedded with biomarker analyses of the tumor and tumor cells in circulation as well in the bone marrow before and after treatment and will also include imaging analyses using a novel positron emission tomography (PET) imaging technology.

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

Official Title
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Pilot Neoadjuvant Trial of Chemohormonal Therapy Followed by Prostatectomy in Patients With High Risk or Oligometastatic Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Degarelix
* Drug: Bicalutamide
* Radiation: Ferumoxytol-enhanced MRI imaging


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix SC + bicalutamide + docetaxel<br>Degarelix SC monthly x3 + bicalutamide 50mg orally QD x 14 wks + Docetaxel 75mg/m2 IV q 21 days x 3 | Drug: Docetaxel<br>* Docetaxel is a commercially marketed product that has been approved by the FDA for the treatment of metastatic prostate cancer. It is also approved for the treatment of other malignant disease, such as locally advanced or metastatic breast cancer that returns after any prior chemotherapy; locally advanced or metastatic non-small cell lung cancer that recurs after prior platinum-based chemotherapy. However, the FDA does not currently approve its use in patients with localized prostate cancer but no evidence of radiographic metastases.<br>* Other names: NSC #628503;Drug: Degarelix<br>* Degarelix is a leuteinizing hormone-releasing hormone (LHRH) antagonist. Degarelix is administered at an initial dose of 240 mg subcutaneously (2 separate injections of 120mg each totaling 240 mg) two weeks prior to cycle 1 day 's 1 treatment with chemotherapy. The initial dose is followed by a maintenance dose of 80mg administered subcutaneously as a single injection every 28 days at cycle 2 day 1 (+/- 7 days) and cycle 3 day 10 (+/- 7 days)<br>* Other names: Degarelix acetate;Drug: Bicalutamide<br>* The dose for bicalutamide tablets therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that bicalutamide tablets be taken at the same time each day. Treatment with bicalutamide tablets should be started at the same time as treatment with an LHRH analog.<br>* Other names: Casodex;|
| Experimental: DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI<br>Degarelix SC monthly x3 + bicalutamide 50mg orally QD x 14 wks + Docetaxel 75mg/m2 IV q 21 days x 3 + Ferumoxytol enhanced MRI within 21 days prior to start of hormonal therapy and second and final ferumoxytol-enhanced MRI at the conclusion of hormone therapy but prior to their prostatectomy. | Drug: Docetaxel<br>* Docetaxel is a commercially marketed product that has been approved by the FDA for the treatment of metastatic prostate cancer. It is also approved for the treatment of other malignant disease, such as locally advanced or metastatic breast cancer that returns after any prior chemotherapy; locally advanced or metastatic non-small cell lung cancer that recurs after prior platinum-based chemotherapy. However, the FDA does not currently approve its use in patients with localized prostate cancer but no evidence of radiographic metastases.<br>* Other names: NSC #628503;Drug: Degarelix<br>* Degarelix is a leuteinizing hormone-releasing hormone (LHRH) antagonist. Degarelix is administered at an initial dose of 240 mg subcutaneously (2 separate injections of 120mg each totaling 240 mg) two weeks prior to cycle 1 day 's 1 treatment with chemotherapy. The initial dose is followed by a maintenance dose of 80mg administered subcutaneously as a single injection every 28 days at cycle 2 day 1 (+/- 7 days) and cycle 3 day 10 (+/- 7 days)<br>* Other names: Degarelix acetate;Drug: Bicalutamide<br>* The dose for bicalutamide tablets therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that bicalutamide tablets be taken at the same time each day. Treatment with bicalutamide tablets should be started at the same time as treatment with an LHRH analog.<br>* Other names: Casodex;Radiation: Ferumoxytol-enhanced MRI imaging<br>* Ferumoxytol-enhanced MRI imaging will evaluate immune micro-environment in the prostate. Three subjects enrolled to the study will undergo the first ferumoxytol-enhanced MRI imaging within 21 days prior to start of hormonal therapy followed by second and final ferumoxytol-enhanced MRI at the conclusion of hormone therapy but prior to their prostatectomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pCR rates | Evaluate the pathologic complete response (pCR) rates in the primary tumor from patients with newly diagnosed locally advanced or oligometastatic prostate cancer treated with combination androgen deprivation therapy (ADT) and 3 cycles of docetaxel chemotherapy followed by prostatectomy. | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PSA | Evaluate the percentage of change in prostate-specific antigen (PSA) from baseline (3 months prior to prostatectomy) to week 6 after prostatectomy in patients with newly diagnosed locally advanced or oligometastatic prostate cancer treated with combination ADT and docetaxel as well as the maximum decline in PSA that occurs at any point during treatment. | From baseline (3 months prior to prostatectomy) to 4-6 weeks after prostatectomy. | 
| PSA Recurrence | Rate of patients with PSA recurrence at month 12 after surgery | Up to 12 months | 
| Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0 | Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Prostatectomy, Chemohormonal therapy, Androgen deprivation therapy, docetaxel chemotherapy