Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer

NCT02560051 | Terminated Phase 2 Results DMC

• 2 other identifiers: GU-13-101HSC-MS-14-0949
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for men who have prostate cancer and have failed local therapy or are not a candidate for prostatectomy or radiation therapy. The purpose of this research study is to assess the safety and benefit of androgen deprivation therapy (ADT, blocks hormones) plus chemotherapy. Degarelix is the hormone blocking drug that will be used. Doxorubicin, Ketoconazole, Docetaxel and Estramustine are the chemotherapy drugs that will be used. The drugs used in this study are approved by the Food and Drug Administration (FDA). Participants will be treated with ADT plus chemotherapy for three, four, or five 8-week cycles (12, 18, or 24 months). The number of cycles of chemotherapy they receive and the number of months they receive ADT will be based on their disease. The current standard treatment is ADT and chemotherapy. What differs in this research study is the cycling and combination of chemotherapy drugs chosen. The drugs chosen for this study have fewer side effects and are believed to provide maximum benefit.

Conditions

Prostatic Neoplasms

Keywords

Prostate Cancer; Advanced; Local Failures

Outcome Measures

Primary Outcomes (1)

• Efficacy as Measured by Number Who Progressed

  Progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements or larger/new lesion

  From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months

Secondary Outcomes (16)

• Efficacy as Measured by Number of Participants With Pathology/Biopsy Positive for Disease

  about 10 months after treatment initiation

• Efficacy as Measured by PSA Level

  baseline

• Efficacy as Measured by PSA Level

  Cycle 1 Day 1, which is the day of treatment initiation

• Efficacy as Measured by PSA Level

  Cycle 2 Day 1, which is about 8 weeks after treatment initiation

• Efficacy as Measured by PSA Level

  Cycle 3 Day 1, which is about 16 weeks after treatment initiation

Study Arms (3)

Definitive local therapy

ACTIVE COMPARATOR

3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)

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

Nodal only/Low-volume bone

ACTIVE COMPARATOR

4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)

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

High volume/no prior tx

ACTIVE COMPARATOR

5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)

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

Interventions

Doxorubicin DRUG

In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week)

Also known as: Adriamycin, Rubex

Definitive local therapy; High volume/no prior tx; Nodal only/Low-volume bone

Ketoconazole DRUG

In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days)

Also known as: Nizoral

Definitive local therapy; High volume/no prior tx; Nodal only/Low-volume bone

Docetaxel DRUG

In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week)

Also known as: Taxotere, Docecad

Definitive local therapy; High volume/no prior tx; Nodal only/Low-volume bone

Estramustine DRUG

In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days)

Also known as: Emcyt

Definitive local therapy; High volume/no prior tx; Nodal only/Low-volume bone

Degarelix DRUG

The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days

Also known as: Firmagon

Definitive local therapy; High volume/no prior tx; Nodal only/Low-volume bone

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 adenocarcinoma of the prostate.
• Patients must belong to one of the following subsets:
• Prior local therapy
• Patients with Prostate Specific Antigen (PSA) recurrence following prostatectomy or radiation therapy who have no radiographic involvement. PSA doubling time ≤6 months.
• Nodal involvement only.
• Low volume bone disease: ≤3 metastases.
• Nodal involvement with associated bone involvement.
• High volume bone-visceral disease: Patients with \>3 metastatic bone sites or visceral metastases.
• No prior definitive local therapy
• Tumors felt to be unresectable, not candidates for radiation therapy, and PSA elevated with biopsy-proven disease.
• Metastatic disease at presentation.
• Patients may have started ADT within 3 months of study entry.
• No previous cytotoxic therapy is allowed, including systemic irradiation with strontium-89, samarium, or radium-223.
• Previous definitive radiotherapy to one metastatic site is acceptable, provided that unirradiated sites remain. At least 8 weeks must have elapsed since radiation therapy to the pelvis. Patients having limited irradiation of a metastatic site are eligible 4 weeks following radiation.
• Patients may have had previous exposure to ADT if it was given for ≤6 months to "downstage" the primary and provided that such therapy was completed at least 12 months prior to entry into this study with a return of serum testosterone to ≥200 ng/dL.

You may not qualify if:

• Patients must not have a second malignancy unless there is confidence of previous curative therapy.
• Patients with a recent history of transient ischemic attack (TIA) (within 6 months), who are requiring regular antianginal therapy, or who are having claudication sufficient to limit activity are not eligible. Patients with a previous history of deep venous thrombosis or pulmonary embolism (within 12 months) are not eligible
• Patients must not have a serious intercurrent medical or psychiatric illness, including serious active infection.
• Patients must not have sensory neuropathy \> grade 1.

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

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

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 of study leading to small number of subjects analyzed

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, DO

  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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director and Professor, Department of Internal Medicine, Division of Oncology

Study Record Dates

• First Submitted: September 17, 2015
• First Posted: September 25, 2015
• Study Start: November 1, 2015
• Primary Completion: September 12, 2017
• Study Completion: September 14, 2017
• Last Updated: November 28, 2018
• Results First Posted: October 11, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)