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

Phase 2

Terminated

Conditions: Prostatic Neoplasms

Interventions: Drug: Doxorubicin
Drug: Ketoconazole
Drug: Docetaxel
Drug: Estramustine
Drug: Degarelix

Registration Number: NCT02560051

Lead Sponsor: The University of Texas Health Science Center, Houston

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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Definitive local therapy	Doxorubicin	3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)
Definitive local therapy	Ketoconazole	3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)
Definitive local therapy	Docetaxel	3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)
Definitive local therapy	Estramustine	3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)
Definitive local therapy	Degarelix	3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix)
Nodal only/Low-volume bone	Ketoconazole	4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)
Nodal only/Low-volume bone	Doxorubicin	4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)
Nodal only/Low-volume bone	Docetaxel	4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)
Nodal only/Low-volume bone	Degarelix	4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)
High volume/no prior tx	Ketoconazole	5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)
Nodal only/Low-volume bone	Estramustine	4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix)
High volume/no prior tx	Doxorubicin	5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)
High volume/no prior tx	Degarelix	5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)
High volume/no prior tx	Docetaxel	5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)
High volume/no prior tx	Estramustine	5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix)

Primary Outcome Measures

Name	Time	Method
Efficacy as Measured by Number Who Progressed	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	Progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements or larger/new lesion

Secondary Outcome Measures

Name	Time	Method
Quality of Life Measure by FACT-P Scale	about 12 weeks after completion of the last cycle	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.
Efficacy as Measured by Number Who PSA Progressed	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	PSA progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements
Efficacy as Measured by Number of Participants With Pathology/Biopsy Positive for Disease	about 10 months after treatment initiation
Safety of Drug Regimen as Measured by Number of Adverse Events	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
Efficacy as Measured by PSA Level	end of treatment, which is about about 8 weeks after the start of the last cycle	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.