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

NCT ID: NCT02494713

Last Updated: 2018-11-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2017-09-14

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.

Detailed Description

This is an open-label, single-arm study of neoadjuvant ADT and chemotherapy in subjects with non-metastatic, locally-advanced prostate cancer who are eligible for radical prostatectomy.

Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy. 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.

The primary endpoint will be complete or near-complete pathologic response.

Safety will be assessed on any patient receiving at least one dose of study drug by the reporting of adverse events, vital signs and by the assessment of findings on physical exam and routine safety laboratory determinations. The severity of adverse events and certain abnormal laboratory findings will be assessed according to the NCI CTCAE V4.03.

Laboratory-based studies will evaluate the following:

• Complete metabolic profile

o BUN, creatinine, alkaline phosphatase, ALT/AST, total bilirubin, LDH, calcium, albumin, glucose, magnesium, uric acid, phosphorous

• Electrolytes

o Sodium, potassium, chloride, CO2 content

• Hematology

• CBC with differential, platelet count
• PT, INR, PTT
• Testosterone
• Biomarkers

• PSA
• CTCs

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ADT + chemotherapy

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.

Group Type: OTHER

Degarelix

Intervention Type: DRUG

Subcutaneous injection, once/month for 4 months

Doxorubicin

Intervention Type: DRUG

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

Ketoconazole

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Estramustine

Intervention Type: DRUG

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

Interventions

Degarelix

Subcutaneous injection, once/month for 4 months

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Ketoconazole

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Estramustine

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

Intervention Type: DRUG

Other Intervention Names

Firmagon; degarelix acetate; Adriamycin; Nizoral; Taxotere; Emcyt

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Robert J Amato

Professor and Director, Division of Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert J Amato, D.O.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

UTHealth Memorial Hermann Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HSC-MS-14-0424

Identifier Type: OTHER

Identifier Source: secondary_id

GU-14-101

Identifier Type: -

Identifier Source: org_study_id