Clinical Trials /

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

NCT03358563

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UW17009
  • SECONDARY ID: 2017-0606
  • SECONDARY ID: A534260
  • SECONDARY ID: SMPH\MEDICINE\HEM-ONC
  • SECONDARY ID: NCI-2017-02428
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: Protocol Version 9/5/2019
  • NCT ID: NCT03358563

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Docetaxeldocetaxel chemotherapy, taxotere, PR 56976, NSC #628503Degarelix SC + bicalutamide + docetaxel
DegarelixDegarelix acetateDegarelix SC + bicalutamide + docetaxel
BicalutamideCasodexDegarelix SC + bicalutamide + docetaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Degarelix SC + bicalutamide + docetaxelExperimentalDegarelix SC monthly x3 + bicalutamide 50mg orally QD x 14 wks + Docetaxel 75mg/m2 IV q 21 days x 3
  • Docetaxel
  • Degarelix
  • Bicalutamide
DegarelixSC+bicalutamide+docetaxel+Ferumoxytol enhanced MRIExperimentalDegarelix 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.
  • Docetaxel
  • Degarelix
  • Bicalutamide

Eligibility Criteria

        Inclusion Criteria:

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

          -  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.

          -  Adequate hematologic and renal function as evidenced by the following within 4 weeks
             of day 1:

               -  ANC >1500/mm3

               -  Hemoglobin (HgB) >10.0 gr/dL independent of transfusion

               -  Platelets >100,000/mm3

               -  Creatinine <2.0 mg/dL

               -  Total bilirubin < Upper Limit of Normal (ULN)

          -  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 (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 >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 (ALT) or aspartate (AST) aminotransferase >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.

          -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in pCR rates
Time Frame:Up to 6 months
Safety Issue:
Description: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 Outcome Measures

Measure:Change in PSA
Time Frame:From baseline (3 months prior to prostatectomy) to 4-6 weeks after prostatectomy.
Safety Issue:
Description: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.
Measure:PSA Recurrence
Time Frame:Up to 12 months
Safety Issue:
Description:Rate of patients with PSA recurrence at month 12 after surgery
Measure:Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0
Time Frame:Up to 6 months
Safety Issue:
Description:Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Trial Keywords

  • Prostate Cancer
  • Prostatectomy
  • Chemohormonal therapy
  • Androgen deprivation therapy
  • docetaxel chemotherapy

Last Updated

October 5, 2020