Hormonal Therapy and Chemotherapy Followed by Prostatectomy in Patients With Prostate Cancer

NCT02494713 | Terminated Phase 2 Results DMC

• 2 other identifiers: GU-14-101HSC-MS-14-0424
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study for men who have locally-advanced prostate cancer and are eligible to undergo prostatectomy. Standard treatment is prostatectomy alone, but there is a chance that cancer may spread to other organs in the future, even after the prostate is removed. If this were to occur, standard treatment would be androgen deprivation therapy (ADT; hormone therapy that blocks testosterone) plus chemotherapy. Clinical trials suggest that neoadjuvant treatment (treatment given before primary therapy) may prevent a recurrence. The purpose of this research study is to assess the safety and benefit of ADT plus chemotherapy given before prostate removal.

Conditions

Prostate Cancer

Keywords

Advanced Prostate Cancer; Neoadjuvant; Hormone therapy; ADT; Androgen Deprivation Therapy; Chemotherapy; Radical Prostatectomy

Outcome Measures

Primary Outcomes (1)

• Efficacy as Measured by Pathologic Response

  Pathologic response is defined by percentage of tumor burden remaining at time of prostate removal. Percentage of tumor burden is measured based on a pathologist's assessment of the prostate tissue removed and visual estimate of how much tumor there is in the prostate.

  Day of prostate removal, which is about 5 months following the day participant signed consent.

Secondary Outcomes (13)

• Efficacy as Measured by Prostate-specific Antigen (PSA) Levels

  baseline

• Efficacy as Measured by Prostate-specific Antigen (PSA) Levels

  Cycle 2 Day 1, about 8 weeks after treatment initiation (but before prostatectomy)

• Efficacy as Measured by Prostate-specific Antigen (PSA) Levels

  Cycle 2 Day 57, about 16 weeks after treatment initiation (but before prostatectomy)

• Efficacy as Measured by Prostate-specific Antigen (PSA) Levels

  Day 133, about 19 weeks after treatment initiation (but before prostatectomy)

• Efficacy as Measured by Prostate-specific Antigen (PSA) Levels

  about 20 weeks after treatment initiation (day of prostatectomy)

Study Arms (1)

ADT + chemotherapy

OTHER

Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy.

Drug: Degarelix; Drug: Doxorubicin; Drug: Ketoconazole; Drug: Docetaxel; Drug: Estramustine

Interventions

Degarelix DRUG

Subcutaneous injection, once/month for 4 months

Also known as: Firmagon, degarelix acetate

ADT + chemotherapy

Doxorubicin DRUG

20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5

Also known as: Adriamycin

ADT + chemotherapy

Ketoconazole DRUG

400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5

Also known as: Nizoral

ADT + chemotherapy

Docetaxel DRUG

35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6

Also known as: Taxotere

ADT + chemotherapy

Estramustine DRUG

280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6

Also known as: Emcyt

ADT + chemotherapy

Eligibility Criteria

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

You may qualify if:

• Pathologic proof of prostatic adenocarcinoma without evidence of regional and/or distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason 8-10) on initial biopsy, clinical stage T2b-T2c with Gleason grade 7 (4+3), or clinical stage T3. No neuroendocrine differentiation or small cell features.
• Recent (\<6 weeks prior to study entry) negative bone scan and CT of the chest and abdomen.
• Appropriate surgical candidate for radical prostatectomy and a performance status of \<2 (ECOG scale).
• Adequate bone marrow function as defined as an absolute peripheral granulocyte count \>1500 and platelet count \>100,000.
• Adequate hepatic function per the following criteria:
• Albumin ≥2.8 g/dL
• AST and ALT ≤5 x ULN
• Total bilirubin \<2 mg/dL
• Adequate renal function per the following criteria:
• o Serum creatinine ≤1.5 x ULN
• Normal coagulation profile (INR ≤ 1.5, aPTT ≤ 1.5 x ULN for the lab) and no history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only (for control of central line patency).
• Age ≥ 18 years
• Written informed consent to participate in this study.

You may not qualify if:

• Prostatic adenocarcinoma with neuroendocrine differentiation or small cell features
• Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1 week of first ADT and chemotherapy treatment
• Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy, or investigational study drug.
• Unable to tolerate multiparametric MRI or is contraindicated.
• Patients not appropriate surgical candidates for radical prostatectomy based on the evaluation of coexistent medical diseases and competing causes of death.
• Patients with uncontrolled cardiac, hepatic, renal, or neurologic/psychiatric disorder.
• Severe gastrointestinal bleeding within 12 weeks of treatment with ADT and chemotherapy
• Patients who are HIV positive or have chronic hepatitis B or C infections.
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a 2D echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months of enrollment demonstrates a left ventricular ejection fraction \>45%.
• Sensory neuropathy grade \>1.
• History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer.
• Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment.
• Any other condition, including concurrent medical condition, social circumstance or drug dependency, which in the opinion of the investigator could compromise patient safety and/or compliance with study requirements

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth Memorial Hermann Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

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

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)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed and limited data.

Results Point of Contact

• Title: Marka Lyons, Research Manager
• Organization: The University of Texas Health Science Center at Houston

Marka.Lyons@uth.tmc.edu

713-500-6919

Study Officials

• Robert J Amato, D.O.

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Division of Oncology

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: July 10, 2015
• Study Start: October 1, 2015
• Primary Completion: September 14, 2017
• Study Completion: September 14, 2017
• Last Updated: November 27, 2018
• Results First Posted: November 27, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)