Clinical trial NCT03358563: Pilot Trial of Chemohormonal Therapy Followed by Prostatectomy in High Risk Prostate Cancer
Official title: Pilot Neoadjuvant Trial of Chemohormonal Therapy Followed by Prostatectomy in Patients With High Risk or Oligometastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Prostatectomy
Chemohormonal therapy
Androgen deprivation therapy
docetaxel chemotherapy
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Prostate Cancer Foundation
First posted: 2017-11-30
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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)

Primary outcomes:
measure: Change in pCR rates
timeFrame: Up to 6 months
Secondary outcomes:
measure: Change in PSA
timeFrame: From baseline (3 months prior to prostatectomy) to 4-6 weeks after prostatectomy.
measure: PSA Recurrence
timeFrame: Up to 12 months
measure: Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0
timeFrame: Up to 6 months
Other outcomes:
measure: Evaluating PSMA PET/MRI imaging
timeFrame: Up to 12 months
measure: Evaluating Response Heterogeneity
timeFrame: Up to 6 months
measure: Change in total tumor burden in individual lesions
timeFrame: Up to 12 months
measure: Evaluating immune microenvironment in prostate with ferumoxytol-enhanced MRI relaxometry
timeFrame: Up to 12 months
measure: Disease progression
timeFrame: Up to 12 months
measure: PSMA PET results and PSA response correlation
timeFrame: Up to 12 months
measure: Evaluate genomic signatures in multifocal prostate cancer after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluate gene expression signatures in multifocal prostate cancer after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluate gene expression signatures in prostate stroma after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluate infiltrating immune cells in prostatectomy specimens after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluating EpCAM-positive disseminated and circulating tumor cells
timeFrame: Up to 12 months
measure: Disseminated and circulating tumor cell analyses versus PSMA PET/MRI and clinical outcomes
timeFrame: Up to 12 months
measure: Evaluate immune microenvironment in bone marrow after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluate secretory profile of stroma after ADT and Docetaxel
timeFrame: Up to 12 months
measure: Evaluate immune microenvironment in prostate after ADT and Docetaxel
timeFrame: Up to 12 months
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Christos Kyriakopoulos, MD
role: PRINCIPAL_INVESTIGATOR
References: