Docetaxel and Degarelix in Treating Patients with Newly Diagnosed Metastatic Prostate Cancer
This phase II trial studies how well docetaxel and degarelix work in treating patients with newly diagnosed prostate cancer that has spread to other places in the body. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Androgen can cause the growth of tumor cells. Hormone therapy using degarelix may fight prostate cancer by lowering the amount of androgen the body makes and/or blocking the use of androgen by the tumor cells. Giving docetaxel and degarelix may work better in treating patients with prostate cancer.
Inclusion Criteria
- Histological or cytological diagnosis of adenocarcinoma of the prostate
- Metastatic disease identified via radiographic assessment by computed tomography (CT) scans of the chest, abdomen, pelvis, and nuclear bone scan; magnetic resonance imaging (MRI) may be used if deemed necessary by the investigator; the CT portion of PET-CT can be used for inclusion in place of dedicated CT chest, abdomen, and pelvis as long as any non-bony lesions of concern are felt by the investigator to be adequately assessed with this imaging; subsequent imaging on protocol should be with dedicated CT chest, abdomen, pelvis unless there are convincing rationale for repeat PET-CT (a bone scan is still required); more specifically, patients must have at least one of the following at time of study enrollment: * Any visceral metastases identified by CT scans, MRI or PET-CT * Site(s) of bony metastasis identified by nuclear bone scan, MRI, PET-CT and/or CT scan * Lymph node based disease not considered to be within a single radiation therapy port (e.g. at or above the aortic bifurcation)
- Non-castrate testosterone level, > 50 ng/dl, at study enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count >= 1,500/mm^3 within 14 days of enrollment to trial
- Hemoglobin >= 8.0 g/dl (may be transfused) within 14 days of enrollment to trial
- Platelet count >= 100,000 mm^3 within 14 days of enrollment to trial
- Creatinine clearance of >= 30 ml/min; creatinine clearance should be determined by the Cockcroft-Gault formula within 14 days of enrollment to trial
- Aspartate aminotransferase (AST) < 2 x institutional upper limit of normal (ULN) within 14 days of enrollment to trial
- Alanine aminotransferase (ALT) < 2 x institutional ULN within 14 days of enrollment to trial
- Total bilirubin =< institutional ULN within 14 days of enrollment to trial
- Agree to use barrier methods of birth control during the docetaxel portion of the protocol and for at least one month after last docetaxel administration
- Informed and must sign and give written informed consent in accordance with institutional and federal guidelines
Exclusion Criteria
- Central nervous system (CNS) metastases (brain or leptomeningeal)
- Osseous metastases felt in the opinion of the clinician to be high-risk for impending pathologic fracture or spinal cord compression
- Active cardiac disease defined as symptomatic congestive heart failure, history of New York Heart Association (NYHA) class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, active angina pectoris, myocardial infarction or coronary intervention within 6 months of registration
- Prior malignancy requiring systemic therapy within the last 5 years except for treated basal or squamous cell skin cancer; history of low-grade malignancies with limited potential to progress as determined by the primary investigator may be enrolled
- Subjects must not have received any previous androgen deprivation therapy (LHRH agonist or LHRH antagonist) or cytotoxic therapy for prostate cancer in the metastatic setting * Exceptions ** Patients may have received no more than 30 days of anti-androgen (e.g. bicalutamide) in the metastatic setting prior to the start of study treatment.
- Subject must not have had more than 36 months of hormonal therapy in combination with prostatectomy or radiation in the setting of localized disease and must not have shown any evidence of disease recurrence within 12 months after stopping hormonal therapy; disease recurrence after hormonal therapy is defined as PSA > 0.2 ng/dl after prostatectomy + hormonal therapy or PSA that is 2.0 ng/dl more than the PSA nadir after radiotherapy + hormonal therapy; previous hormonal therapy to the prostate must have stopped at least 12 months prior to enrollment
- Subjects must not have been treated with prior docetaxel in the setting of metastatic prostate cancer; subjects may have been treated with docetaxel in the setting of localized prostate cancer (likely as a trial-based neoadjuvant or adjuvant approach to prostatectomy or radiation); subjects treated with this approach must not have shown any evidence of disease recurrence within 12 months after stopping docetaxel; disease recurrence after docetaxel is defined as PSA > 0.2ng/dl after prostatectomy + docetaxel or PSA that is 2.0ng/dl more than the PSA nadir after radiotherapy +docetaxel; previous docetaxel in the setting of localized prostate cancer must have stopped at least 12 months prior to study enrollment
- Palliative radiation therapy may have been received but not within the 30 days prior to study treatment
- Presence of peripheral neuropathy > grade 1
- Known human immunodeficiency virus (HIV)-positive
- Presence of any severe or uncontrolled concurrent medical condition felt in the opinion of the investigator to increase the risk of serious toxicity from the study therapy
- Prior hypersensitivity to any of the components of the study drugs
Additional locations may be listed on ClinicalTrials.gov for NCT03069937.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine the proportion of men with newly diagnosed metastatic hormone sensitive prostate cancer who obtain and maintain a prostate-specific antigen (PSA) complete response (less than or equal to 0.2 ng/ml) at 10 months (40 weeks) after initiation of trial therapy (7 months of androgen deprivation therapy) with four cycles of upfront docetaxel chemotherapy without androgen deprivation therapy followed by two additional cycles of docetaxel concurrent with androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) antagonist degarelix and then ongoing degarelix.
SECONDARY OBJECTIVES:
I. To determine the proportion of men with newly diagnosed metastatic hormone sensitive prostate cancer who obtain and maintain a PSA complete response (less than or equal to 0.2 ng/ml) at 6 months (28 weeks) after initiation of trial therapy with four cycles of upfront docetaxel chemotherapy without androgen deprivation therapy followed by two additional cycles of docetaxel concurrent with androgen deprivation therapy with LHRH antagonist degarelix and then ongoing degarelix.
II. To assess the toxicity of administering four cycles of docetaxel chemotherapy without androgen deprivation therapy followed by two additional cycles of docetaxel concurrent with androgen deprivation therapy with degarelix in non-castrate men with newly diagnosed metastatic hormone-sensitive prostate cancer.
III. To determine the frequency of disease progression (clinical, radiographic, or PSA as outlined in this protocol), if any, during the four cycles of upfront docetaxel.
IV. To determine the frequency of PSA response during the four cycles of upfront docetaxel.
V. To determine the time to development of castration resistance after initiation of antiandrogen therapy (ADT) with degarelix for the cohort as a whole during the entire course of therapy.
VI. To determine the progression-free survival and overall survival of the patients treated with upfront docetaxel followed by ADT.
EXPLORATORY OBJECTIVES:
I. To determine whether baseline tumoral genomic changes assessed via a serum assay of cell-free tumor deoxyribonucleic acid (DNA) correlate with responses to trial therapy.
II. To evaluate PSA kinetics over time over the duration of study therapy.
OUTLINE:
Patients receive docetaxel intravenously (IV) over 60 minutes on day 1 and degarelix subcutaneously (SC) on day 1 of cycle 5 and day 8 of cycle 6. Treatment for docetaxel repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Cycles with degarelix repeat every 28 days for up to 10 months (40 weeks) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMedical University of South Carolina
Principal InvestigatorTheodore Stewart Gourdin
- Primary ID102509
- Secondary IDsNCI-2017-01130
- ClinicalTrials.gov IDNCT03069937