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

NCT03358563 | Completed Early Phase 1 DMC FDA Drug

• 6 other identifiers: UW170092017-0606A534260SMPH\MEDICINE\HEM-ONCNCI-2017-02428Protocol Version 1/18/2022
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in PSA

  From baseline (3 months prior to prostatectomy) to 4-6 weeks after prostatectomy.

• PSA Recurrence

  Up to 12 months

• Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0

  Up to 6 months

Other Outcomes (15)

• Evaluating PSMA PET/MRI imaging

  Up to 12 months

• Evaluating Response Heterogeneity

  Up to 6 months

• Change in total tumor burden in individual lesions

  Up to 12 months

Study Arms (2)

Degarelix SC + bicalutamide + docetaxel

EXPERIMENTAL

Degarelix SC monthly x3 + bicalutamide 50mg orally QD x 14 wks + Docetaxel 75mg/m2 IV q 21 days x 3

Drug: Docetaxel; Drug: Degarelix; Drug: Bicalutamide

DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI

EXPERIMENTAL

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; Drug: Degarelix; Drug: Bicalutamide; Radiation: Ferumoxytol-enhanced MRI imaging

Interventions

Docetaxel DRUG

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.

Also known as: docetaxel chemotherapy, taxotere, PR 56976, NSC #628503

Degarelix SC + bicalutamide + docetaxel; DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI

Degarelix DRUG

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)

Also known as: Degarelix acetate

Degarelix SC + bicalutamide + docetaxel; DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI

Bicalutamide DRUG

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.

Also known as: Casodex

Degarelix SC + bicalutamide + docetaxel; DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI

Ferumoxytol-enhanced MRI imaging RADIATION

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.

DegarelixSC + bicalutamide + docetaxel + Ferumoxytol enhanced MRI

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• United States Department of Defense: collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center Homepage

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Christos Kyriakopoulos, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: November 30, 2017
• Study Start: January 17, 2018
• Primary Completion: August 10, 2021
• Study Completion: September 2, 2022
• Last Updated: May 3, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)