Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Androgen Ablation; Cabazitaxel; Salvage Therapy; Neoadjuvant Treatment - Hormonal Therapy; Neoadjuvant Treatment - Cabazitaxel
Intervention description: All patients will receive luteinizing hormone-releasing hormone (LHRH) agonist therapy (leuprolide or goserelin acetate) concurrent with Cabazitaxel, before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.; Intravenous treatment with Cabazitaxel 25 mg/m^2 is given on day 1 every 21 days. A cycle of chemotherapy will be defined as 21 days. A total of four cycles of combination therapy are planned for a total duration of 12 weeks (before surgery), starting within 3 weeks of protocol entry, to be given concurrent with hormone therapy.; Patients will undergo 4 cycles of chemotherapy in conjunction with LHRH agonist therapy (before surgery) subsequent to which they will have their serum Prostate-specific antigen (PSA), bone scan, abdominal pelvic computed tomography (CT) or magnetic resonance imaging (MRI) repeated. Patients with a detectable metastatic diseases will be removed from the study. Salvage surgery will be performed within 8 weeks after the completion of Cabazitaxel chemotherapy. For patients who achieved undetectable PSA following surgery, androgen deprivation therapy will be discontinued.; All treatment will be given on an outpatient basis. Treatment should start within 3 weeks of protocol entry. All patients will receive androgen ablation with LHRH agonist therapy in conjunction with the 4 cycles of Cabazitaxel for neoadjuvant chemohormonal therapy. Androgen ablative therapy will be discontinued before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.; All treatment will be given on an outpatient basis and should start within 3 weeks of protocol entry. Intravenous treatment with Cabazitaxel is given on Day 1 every 3 weeks. A cycle of combination therapy will be defined as 3 weeks. A total of 4 cycles of combination therapy are planned before surgery for a total duration of 12 weeks.
Cabazitaxel will be administered before surgery by one-hourly infusions via central or peripheral intravenous access at a dose of 25 mg/m^2 as a one hour intravenous infusion in combination with oral prednisone 10 mg administered daily throughout Cabazitaxel treatment. It is advised that all patients receiving Cabazitaxel have a reliable form of venous access, e.g., central venous catheter to ensure their ability to receive therapy without undue delay.
Intervention MeSH terms: Leuprolide; Goserelin; Bicalutamide; Androgens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent; high risk

Summary:

      The aim of this study is to test whether adding chemotherapy/cabazitaxel and
      hormonal/androgen deprivation therapy before surgical removal of your prostate would improve
      the outcome of salvage surgery for locally recurrent prostate cancer after the initial
      primary radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy must be more than 10 years

          -  Peripheral neuropathy: must be </= grade 1

          -  A minimum PSA of 1 ng/ml if not on androgen deprivation therapy

          -  Patients must have one of the following criteria to be eligible:

               -  PSA recurrence with a doubling time of less than 9 months (calculated by at least
                  3 PSA values that were obtained at least 4 weeks apart)

               -  Prostatic biopsy Gleason Grade of >/= 8 at the time of initial biopsy prior to
                  radiation therapy and as determined by either an outside pathology report or on
                  review of slides by our institutional pathologist(s)

               -  Clinical stage of >/= T3 (defined as evidence of extracapsular or seminal vesicle
                  extension on digital rectal examination or transrectal ultrasonography) either at
                  the time of initial diagnosis or following radiotherapy

          -  Prior radiation therapy of any type including external beam radiotherapy,
             brachytherapy, high dose radiotherapy, or proton therapy

          -  Positive prostate biopsy documenting local recurrence following radiation therapy

          -  Prior androgen deprivation therapy up to a total duration of 36 months is allowable.

          -  Patients who are on LHRH analog therapy should continue such therapy provided that the
             patient does not have castration resistant prostate cancer (rising PSA in the presence
             of castrate levels of serum testosterone, ie < 50 ng/dl). Androgen deprivation therapy
             other than LHRH analog should be discontinued 4 weeks prior to study enrollment.

          -  All prostatic carcinoma variants except small cell carcinoma of the prostate will be
             allowed.

          -  Patients must have no evidence of metastatic diseases on the bone scan and an
             abdominal/pelvic CT or MRI performed within 30 days of study enrollment.

          -  All patients must be regarded as acceptable anesthetic risk for salvage surgery
             (salvage radical prostatectomy, salvage cystoprostatectomy, salvage total pelvic
             exenteration) and confirm their intention to undergo salvage surgery at the end of the
             neoadjuvant chemohormonal therapy.

          -  Patients must have adequate bone marrow function defined as an absolute peripheral
             granulocyte count of > 1,500/mm^3 and platelet count of > 100,000/mm^3; adequate
             hepatic function defined with a total bilirubin of < 1.5 mg/dl and aspartic
             transaminase/alanine transaminase (AST/ALT) < 1.5 X the upper limits of normal (ULN);
             adequate renal function defined as serum creatinine clearance > 60 ml/min (measured or
             calculated).

          -  Men and women of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

          -  Patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study, in keeping with the policies of the institution.

          -  All patients must be evaluated in the Department of Genitourinary Oncology prior to
             signing informed consent.

        Exclusion Criteria:

          -  Patients with small cell histology

          -  Patients with clinical, radiological, or pathological evidence of bone, lymph node or
             visceral metastasis (liver or lung metastasis)

          -  Castration resistant prostate cancer defined as rising PSA profile in setting of
             castrate levels of testosterone (serum testosterone < 50 ng/dl)

          -  Prior chemotherapy

          -  Patients with severe or uncontrolled intercurrent infection

          -  Patients with New York Heart Association (NYHA) Class III/IV congestive heart failure,
             unstable angina or history of myocardial infarction within the last 6 months

          -  Contraindications to corticosteroids

          -  Uncontrolled severe hypertension, persistently uncontrolled diabetes mellitus, oxygen
             dependent lung disease, chronic liver disease or HIV infection

          -  Second malignancies (excluding non-melanoma skin cancer) unless disease-free for 3
             years

          -  Overt psychosis, mental disability or otherwise incompetent to give informed consent

          -  Patients with a history of severe hypersensitivity reaction to Cabazitaxel® or other
             drugs formulated with polysorbate 80