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About
This phase II trial studies how well giving testosterone at levels higher than normally found in the body (supraphysiological) works to enhance chemotherapy treatment in patients with prostate cancer that has progressed despite being previously treated with androgen therapies and has spread from where it first started (prostate) to other places in the body (metastatic castration-resistant prostate cancer). In patients that have developed progressive cancer in spite of standard hormonal treatment, administering supraphysiological testosterone may result in regression of tumors by causing deoxyribonucleic acid (DNA) damage in tumor cells that have adapted to low testosterone conditions. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Giving supraphysiological levels of testosterone and carboplatin or etoposide together may be an effective treatment for metastatic castration-resistant prostate cancer.
Full description
OUTLINE: Patients are randomized to 1 of 2 cohorts.
COHORT I: Patients are then assigned to 1 of 3 sub-cohorts within cohort I.
COHORT Ia: Patients continue to receive ADT and receive testosterone cypionate intramuscularly (IM) on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin intravenously (IV) on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT Ib: Patients continue to receive ADT and receive carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT Ic: Patients continue to receive ADT and receive testosterone cypionate IM and carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients are then assigned to 1 of 3 sub-cohorts within cohort II.
COHORT IIa: Patients continue to receive ADT and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide orally (PO) once daily (QD) on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT IIb: Patients continue to receive ADT and receive etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT IIc: Patients continue to receive ADT and receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All patients undergo a biopsy on study and blood sample collection on study, and bone scans and computed tomography (CT) scans throughout the trial. Patients may also undergo an optional second biopsy at the end of study treatment.
After completion of study treatment, patients are followed up at 30 days, and then every 6 months for 2 years.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Involvement in the planning and/or conduct of the study
Other malignancy unless curatively treated with no evidence of disease for >= 2 years except: adequately treated non-melanoma skin cancer, non-muscle invasive bladder cancer
Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade > 2) caused by previous cancer therapy, excluding alopecia
Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
Use of corticosteroids at a dose equivalent to > 10 mg of prednisone daily
Planning to receive concurrent treatment with another systemic cancer therapy, aside from a luteinizing hormone releasing hormone (LHRH) analogue
Use of warfarin is not permitted. Low-molecular weight heparin and direct oral anticoagulants are allowed, but their use should be discussed with the principal investigator (PI) first
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, history of prior myocardial infarction, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure [BP] >= 165/100), history of prior stroke, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease or any psychiatric disorder that prohibits obtaining informed consent
Patients with a known hypersensitivity to the testosterone cypionate, etoposide, carboplatin or any of the excipients of these products
Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
Evidence of disease that, in the opinion of the investigator, would put the patient at risk from testosterone therapy (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
Patients with pain attributable to their prostate cancer.
Tumor causing urinary outlet obstruction that requires catheterization for voiding. Patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll. Patients with percutaneous nephrostomy tubes will also be permitted to enroll
Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation.
Patients with NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within 5 years of enrollment to the study.
Primary purpose
Allocation
Interventional model
Masking
46 participants in 6 patient groups
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Central trial contact
Michael Schweizer
Data sourced from clinicaltrials.gov
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