Degarelix, Bicalutamide, and Docetaxel before Surgery in Treating Patients with High Risk Metastatic Prostate Cancer

Status: Active

Description

This pilot early phase I trial studies how well degarelix, bicalutamide, and docetaxel before surgery works in treating patients with high risk prostate. Hormone therapy using degarelix and bicalutamide, may fight prostate cancer by lowering the amount of testosterone the body makes. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving degarelix, bicalutamide, and docetaxel before surgery may work better in treating patients with prostate cancer.

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 > 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
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (within 4 weeks of day 1)
  • Hemoglobin (HgB) >= 10.0 gr/dL independent of transfusion (within 4 weeks of day 1)
  • Platelets >= 100,000/mm^3 (within 4 weeks of day 1)
  • Creatinine =< 2.0 mg/dL (within 4 weeks of day 1)
  • Total bilirubin =< upper limit of normal (ULN) (within 4 weeks of day 1)
  • Estimated life expectancy of >= 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 (e.g., 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
  • Total bilirubin > ULN (NOTE: in subjects with Gilbert’s syndrome, if total bilirubin is > ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) or
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.0 x ULN or
  • ALT or aspartate AST > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN
  • Peripheral neuropathy grade > 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

Locations & Contacts

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Christos Kyriakopoulos
Phone: 608-263-7107
Email: ckyriako@medicine.wisc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. 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.

SECONDARY OBJECTIVES:

I. Evaluate the percentage of change in prostate-specific antigen (PSA) from baseline to week 4 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.

II. Rate of patients with PSA recurrence at month 12 after surgery.

III. Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel.

EXPLORATORY OBJECTIVES:

I. Evaluate prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) imaging as a method for determining treatment response in primary prostate cancer and metastatic lesions after ADT and docetaxel.

II. Evaluate heterogeneity of response in multifocal prostate lesions at the time the primary objective is assessed.

III. Evaluate change in total tumor burden in individual lesions and across all lesions over time for each patient.

IV. Correlate disease progression on MRI, technetium Tc 99m medronate (99mTc-MDP) bone scintigraphy and computed tomography (CT) scans with PSMA uptake measures.

V. Correlate PSMA PET results with PSA response and time to PSA progression.

VI. Evaluate genomic signatures in multifocal prostate cancer after ADT and docetaxel.

VII. Evaluate gene expression signatures in multifocal prostate cancer after ADT and docetaxel.

VIII. Evaluate gene expression signatures in prostate stroma after ADT and docetaxel.

IX. Evaluate infiltrating immune cells in prostatectomy specimens after ADT and docetaxel.

X. Evaluate epithelial cell adhesion molecule (EpCAM)-positive disseminated and circulating tumor cells for subcellular localization of the androgen receptor and glucocorticoid receptor.

XI. Correlate disseminated and circulating tumor cell analyses with the PSMA PET/MRI measures and clinical outcomes.

XIl. Evaluate immune microenvironment in bone marrow after ADT and docetaxel.

XIII. Evaluate secretory profile of stroma after ADT and docetaxel.

OUTLINE:

Patients receive degarelix subcutaneously (SC) every 4 weeks for 3 doses (2 weeks before course 1, day 1 [pre-course]; course 2, day 1; and course 3, day 10), bicalutamide orally (PO) once daily (QD) for up to 14 weeks, and docetaxel intravenously (IV) over 1 hour on day 1. Treatment repeats every 21 days for 3 courses (docetaxel) in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy 3-7 weeks after the last dose of docetaxel.

After completion of study treatment, patients are followed up at 4-6 weeks, and then every 3 months for 1 year.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Christos Kyriakopoulos

Trial IDs

Primary ID UW17009
Secondary IDs NCI-2017-02428, 2017-0606
Clinicaltrials.gov ID NCT03358563