Vinflunine in Hormone Refractory Prostate Cancer (HRPC)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Vinflunine
Intervention description: Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Hormone Refractory; Vinflunine; Salvage Chemotherapy

Summary:

      Currently, there are no established 2nd-line or salvage chemotherapy regimens for patients
      with HRPC, many of whom retain an excellent performance status. The antitumor characteristics
      and toxicity profile of vinflunine make it an ideal agent to be investigated in this setting.
      In this Phase II trial, we plan to evaluate the efficacy, toxicity, and feasibility of
      administering IV vinflunine at a dose of 320 mg/m2 q3w as salvage chemotherapy in patients
      with HRPC. The patients will be evaluated for response, survival, and toxicity. If
      significant antitumor activity is demonstrated, further evaluation of this agent either alone
      or combination regimens and at earlier stages of disease will be indicated.
    

Eligibility criteria:

        Inclusion Criteria:

        Men age 18 years of age or older who have HRPC are eligible for this study based on the
        following inclusion criteria:

          1. Histologically confirmed adenocarcinoma of the prostate.

          2. Progressive hormone refractory locally advanced or metastatic disease.

               -  (Definition of HRPC): Clinical or serological evidence of disease progression
                  despite adequate anti-androgen therapy, documented by castrate levels of serum
                  testosterone (<50 ng/mL).

               -  Patients on medical castration therapy should continue on treatment to maintain
                  castrate levels of serum testosterone. Patients receiving anti-androgen or
                  estrogen therapy should either be maintained on it, or have documented
                  progression 4 weeks after withdrawal of all agents (except nilutamide and
                  bicalutamide), which requires 6 weeks.

          3. Disease Progression, documented by any of the following:

               -  PSA Progression, documented by an elevated PSA level (>5 ng/mL), which has risen
                  serially from the baseline PSA value (PSA value #1) on two occasions, each at
                  least 1 week apart (these will be considered PSA values #2 and #3). (Note: if the
                  level of PSA value #3 is less than the level of PSA value #2, a subsequent PSA
                  value must be obtained (PSA value #4) at least 1 week after PSA value #3 was
                  measured. In order for this event to be considered a PSA progression, the level
                  of this final PSA value (PSA value #4) must be greater than the PSA level that
                  was observed for PSA value #2.

               -  Progressive metastatic prostate carcinoma, documented by computed tomography
                  (CT), magnetic resonance imaging (MRI), or radiograph of non osseous lesions (see
                  Section 7.2).

               -  Bone Scan Progression, documented by the appearance of at least one or more new
                  lesions that are not believed to be secondary to tumor flare phenomenon.

          4. Patients with bone only disease must have a PSA level >=5 ng/mL; patients with stable
             lesions must have evidence of PSA progression. Patients must have radiographically or
             clinically demonstrable metastatic disease.

          5. Receipt of either 1 or 2 previous chemotherapy regimens; one of these regimens must
             have included docetaxel.

          6. ECOG performance status of 0-2.

          7. Adequate bone marrow function, defined by: white blood cells >=3,500/uL, hemoglobin
             >=8 g/dL, platelet count >=100,000/uL.

          8. Adequate renal function, defined by: serum creatinine <1.8 mg/dL, or calculated or
             measured creatinine clearance (GFR) of >=60 cc/min. Patients with a creatinine
             clearance of >30 mL/min but <60 mL/min may also be enrolled, but will require an
             initial adjusted dose (see Section 5.1)

          9. Adequate hepatic function, defined by: total bilirubin <1.5 x the upper limit of
             normal, AST <2 x the upper limit of normal.

         10. Patients must be able to comprehend the nature of the study and provide written
             informed consent.

         11. Partners of women of childbearing potential must use effective contraception while on
             treatment and for at least 3 months thereafter. Women of childbearing potential
             include females who have experienced menarche and have not undergone successful
             surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral
             oophorectomy) or are not post-menopausal (i.e., amenorrhea >12 months).

         12. Patients on bisphosphonate therapy (at the discretion of the investigator).

        Exclusion Criteria:

          1. History of other prior malignancy in the past 5 years (excluding resected basal cell
             or squamous cell skin cancer).

          2. History of second- or third-degree heart block, uncontrolled angina, uncontrolled
             hypertension, or recent myocardial infarction or congestive heart failure (New York
             Heart Association Class III-IV) within the past 6 months (see Appendix F)

          3. Cerebral vascular accident within the past 6 months.

          4. Peripheral neuropathy > grade 2 per Common Terminology Criteria for Adverse Events
             (CTCAE) v3.0.

          5. Patients with rising PSA but no demonstrable metastases.

          6. Previous radiotherapy, outside of standard portals, utilized for prostate cancer (if
             total amount of radiotherapy encompasses >25% of bone marrow containing osseous
             regions).

          7. Prior therapy with Strontium 90, Samarium 150, or other injectable therapeutic
             radioisotopes.

          8. History of prior allergic reaction to any vinca alkaloid.

          9. Use of chemotherapy or investigational drugs within 4 weeks prior to the first dose of
             study drug.

         10. Treatment with ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir within
             4 weeks prior to the first dose of study drug.

         11. Previous treatment with an anthracycline.

         12. Patients who are unable to receive chemotherapy on a basis of once every three weeks
             as a result of physical, environmental, or co existent medical problems.