Cabazitaxel and Radiation For Patients With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Cabazitaxel
Intervention description: Dose Level Day 1, 22, 43
5.0 mg/m2
10.0 mg/m2
15.0 mg/m2
20.0 mg/m2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Radical prostatectomy

Summary:

      There is a high relapse rate for patients who have undergone prostatectomy and have
      pathologic extracapsular prostate extension, positive surgical margins or seminal vesicle
      involvement (pathologic stage 3 disease). While adjuvant radiation improves progression-free
      and overall survival, approximately half of these patients will develop recurrence.
      Similarly, radiation therapy has become the standard salvage therapy for patients with rising
      PSA >0.1 - < 2.0 ng/mL. In common solid tumors such as NSCLC, head and neck cancer and upper
      gastrointestinal cancers, the addition of chemotherapy to radiation improves survival. It is
      hypothesized that the addition of radiosensitizing chemotherapy to standard adjuvant
      radiation will improve survival in patients with stage 3 prostate cancer after prostatectomy
      and patients with rising PSA < 2.0 ng.mL without detectable disease. Taxanes are powerful
      radiation enhancers since they synchronize tumor cells in G2/M the most radiosensitive phase
      of the cell cycle.17,18 Cabazitaxel is the most active taxane in the treatment of prostate
      cancer. Therefore, we propose a phase I study establishing the optimal dose of cabazitaxel
      with adjuvant radiation for stage 3 prostate cancer after prostatectomy (PSA undetectable - <
      2.0 ng/mL). and for patients with persistent or rising PSA post prostatectomy (PSA >0.1 - <
      2.0 ng/mL).
    

Eligibility criteria:

        Conditions for Patient Eligibility

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

          -  Radical prostatectomy for adenocarcinoma of the prostate with at least one of the
             following:

               -  Extracapsular tumor extension,

               -  Positive surgical margins,

               -  Seminal vesicle invasion

               -  Regional lymph node positive (N1)

               -  Post-prostatectomy PSA of > 0.1 - < 2.0 ng/mL at least 6 weeks after
                  prostatectomy and within 30 days of registration in a patient with T2 or T3
                  disease at prostatectomy.

          -  No distant metastases.

          -  No prior pelvic or prostate radiation or chemotherapy for prostate cancer.

          -  ECOG performance status 0-1.

          -  Age>18.

          -  Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥
             1500 cells/mm3; platelet count ≥100,000 cells/mm3, Creatinine ≤ 1.5X upper limit of
             normal (if creatinine clearance 1.0-1.5x ULN, creatinine clearance will be calculated
             according to Chronic Kidney Disease Epidemiology Group formula and patients with
             creatinine clearance < 60 ml/min should be excluded),19 .Hgb > 9.0 g/dl, total
             bilirubin ≤ 1x ULN, and AST or ALT ≤ 2.5 x ULN.

          -  Life expectancy of at least 1 year.

          -  Must not have uncontrolled severe, intercurrent illness.

          -  No concurrent anticancer therapy.

          -  Men of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

          -  Signed study-specific consent form prior to study entry.

          -  Conditions for Patient Ineligibility

        Patients meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Evidence of distant metastases (M1). Equivocal bone scans are allowed if plain films
             are negative for metastasis.

          -  Major medical or psychiatric illness which, in the investigator's opinion, would
             prevent completion of treatment and would interfere with follow-up.

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 2 years (For example, carcinoma in situ of the oral cavity or bladder
             are permissible).

          -  History of severe hypersensitivity (> grade 3) reaction to Cabazitaxel or other drugs
             formulated with polysorbate 80.

          -  History of severe hypersensitivity (> grade 3) to docetaxel.

          -  Any uncontrolled severe, intercurrent illness (including uncontrolled diabetes)

          -  At least 4 weeks since any major surgery.

          -  Patients on concurrent anticancer therapy.

          -  PSA > 2ng/ml

          -  Concurrent or planned treatment with strong inhibitors or inducers of cytochrome p450
             3A4/5 (a one-week wash out period is necessary for patients who are already on these
             treatments (see appendix H and I)

          -  Androgen deprivation therapy started prior to prostatectomy for > 6 months duration;

          -  Neoadjuvant chemotherapy prior to prostatectomy;

          -  Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the
             primary treatment and not a salvage procedure;

          -  Prior pelvic radiotherapy;