Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Prostate Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 11/30/2018 |
| Start Date: | November 2015 |
| End Date: | September 14, 2017 |
Phase 2 Study of Androgen Deprivation Therapy (ADT) Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer
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.
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.
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.
Inclusion criteria:
- 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.
- Patients must be free of serious comorbidity and have a life expectancy of ≥3 years.
- Patients must have adequate physiologic reserves as evidenced by:
- Eastern Cooperative Oncology Group (ECOG) status of ≤2.
- Patients must have adequate bone marrow function: Platelets ≥100,000 cells/mm3,
Hemoglobin ≥9.0 g/dL, and Absolute Neutrophil Count (ANC) ≥1,500 cells/mm3.
- Patients must have adequate renal function: creatinine ≤2 × upper limit of normal
(ULN).
- Patients must have adequate liver function: Aspartate aminotransferase (AST) / Alanine
transaminase (ALT) ≤2.5 × ULN; alkaline phosphatase <2.5 × ULN, unless bone metastasis
is present in the absence of liver metastasis; and bilirubin < ULN or 1.5 mg/dl.
- No evidence of active ischemia on electrocardiogram (ECG) and documentation of
ejection fraction (EF) ≥50%.
Exclusion criteria:
- 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.
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