Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Docetaxel

Androgens

Doxorubicin

Liposomal doxorubicin

Hormones

Ketoconazole

Estramustine

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Hormonal

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

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

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

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)

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

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)

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

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

Degarelix

Robert J Amato, DO

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.

As a working hypothesis, investigators suspect that the transformation from an androgen-dependent to an androgen-independent phenotype is mediated by expansion of an androgen-independent clone already present at the time of ADT that continues to grow while androgen-sensitive clones are being suppressed. It is thus desirable to bring treatment to bear on the androgen-independent component while the corresponding tumor burden remains minimal and prolong the time to hormone resistance. Investigators view the androgen-independent component as analogous to "microscopic residual" or "micro-metastatic" disease, for which adjuvant chemotherapy has been shown to be effective in other contexts, even when the same drugs had little or no impact on survival in the setting of more advanced disease.

By treating all components of the tumor initially, investigators anticipate that the emergence of androgen-independent growth will be delayed, ultimately prolonging patient survival. Additionally, instead of treating patients empirically with an identical regimen, as in investigator's previous work, these patient subsets were designed to ensure a level of treatment appropriate to their individual disease, thus potentially lessening the burden of treatment (such as the long-term adverse effects of ADT). Investigators have chosen 3, 4, or 5 cycles of chemotherapy to be administered on the basis of tumor burden, a treatment selection method long established in germ cell tumors and used by this PI. Sub-analyses of previous data have raised the concern that treating patients with varying levels of disease the same way does not produce optimal results. Therefore, investigators seek to improve outcomes by tailoring treatment to tumor burden. In this study, patients with less tumor burden will receive 3 cycles of chemotherapy and 12 months of ADT, those with moderate tumor burden will receive 4 cycles and 18 months of treatment, and those with the greatest tumor burden will receive 5 cycles and 24 months of treatment. Additionally, this regimen of administering treatment sequentially, including a 2-week break, reduces toxicity.

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

Phase 2 Study of Androgen Deprivation Therapy (ADT) Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer

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

Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

The time point is the end of treatment, which is about about 8 weeks after the start of the last cycle. For the arm completing 3 cycles, the time point is 24 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 32 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 40 weeks after treatment initiation.

PSA progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL.

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL.

The time point is about 12 weeks after completion of the last cycle. For the arm completing 3 cycles, the time point is 36 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 44 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 52 weeks after treatment initiation.

The University of Texas Health Science Center, Houston

Director and Professor, Department of Internal Medicine, Division of Oncology

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

Doxorubicin: 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)

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

Docetaxel: 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)

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

Degarelix: 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

Definitive Local Therapy

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

Doxorubicin: 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)

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

Docetaxel: 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)

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

Degarelix: 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

Nodal Only/Low-volume Bone

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

Doxorubicin: 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)

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

Docetaxel: 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)

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

Degarelix: 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

High Volume/no Prior tx

Total

Age, Continuous

Sex: Female, Male

African American

Caucasian

Hispanic

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

The Eastern Cooperative Oncology Group (ECOG) Performance Status scale measures level of functioning. The scale ranges from 0 to 5, with 0 indicating the highest level of functioning and 5 the lowest.

ECOG Performance Status

Early termination of study leading to small number of subjects analyzed

Marka Lyons, Research Manager

Efficacy as Measured by Number Who Progressed

Fewer were analyzed than the number that started or completed the study because not all participants were biopsied following treatment.

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

Efficacy as Measured by PSA Level

Fewer were analyzed than the number that started study because not all participants completed the full number of cycles of treatment assigned. For some participants treatment was prematurely discontinued at different points through the course of treatment because of adverse events, progression, and participant withdrawal from study.

This time point is after 4 cycles of chemotherapy so no one in group "definitive local therapy" were analyzed. For the other groups fewer were analyzed than the number that started study because for some participants treatment was prematurely stopped at different points in treatment because of adverse events, progression, and withdrawal from study.

This time point is after 5 cycles of chemo so so no participants in the groups that had only 3/4 cycles were included. For the other group fewer were analyzed than the number that started study because for some treatment was prematurely stopped at different points in treatment because of adverse events, progression, and withdrawal from study.

Fewer were analyzed than the number that started study because some participants were taken off study at different points in treatment or follow-up because of adverse events, progression, and withdrawal from study.

Efficacy as Measured by Number Who PSA Progressed

Quality of Life Measure by FACT-P Scale

Fewer were analyzed than the number that started study because some participants were taken off study at different points throughout the study because of adverse events, progression, and participant withdrawal from study. Additionally, some participants did not wish to complete the FACT-P questionnaire.

This is after 4 cycles of chemo so no one in group "definitive local therapy" were analyzed. For the other groups fewer were analyzed than the number that started study because for some participants treatment or follow-up was prematurely stopped at different points because of adverse events, progression, and withdrawal from study.

Spots Global Cancer Trial Database for local failures