Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment
Condition: Metastatic Castration-resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Carfilzomib; Dexamethasone; Acyclovir
Intervention description: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.; Administered prior to administration of Study drug; Administered orally twice daily
Intervention MeSH terms: Acyclovir; Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: Male
Minimum age: 19 Years
Healthy volunteers: No
Keywords: carfilzomib; prostate cancer; PSA (prostate-specific antigen); CRPC (castration-resistant prostate cancer)

Summary:

      This study will test how effective the drug, Carfilzomib, reduces progression of prostate
      cancer in patients who have previously received chemotherapy and androgen inhibitors.
      Carfilzomib is approved for multiple myeloma but is not approved for prostate cancer.
      Therefore, it is considered investigational. Other approved methods of treatment for
      metastatic prostate cancer have demonstrated only modest benefits. Novel and tolerable agents
      are necessary to make further gains and extend overall survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven adenocarcinoma of the prostate

          -  Metastatic disease

          -  Progressive disease (PSA, radiologic, symptomatic) following abiraterone acetate
             and/or Enzalutamide (prior sipuleucel-T and chemotherapy are allowed); PSA progression
             is defined as baseline increase followed by any PSA increase ≥1 week apart.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

          -  Patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to
             one of the following: practice effective barrier contraception during the entire study
             treatment period and through a minimum of 30 days after the last dose of study drug,
             or completely abstain from heterosexual intercourse if female partner of childbearing
             age.

          -  An elevated PSA level of >2ng/mL for patients progressing by PSA criteria is required
             (last confirmatory sample must be >2ng/mL)

          -  Currently on androgen ablation hormone therapy (a luteinizing hormone- releasing
             hormone (LHRH) agonist/antagonist or orchiectomy) with testosterone level <50ng/dL)

          -  Has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2

          -  Left ventricular ejection fraction (LVEF) ≥40% on 2-D transthoracic echocardiogram
             (ECHO); Multi-gated Acquisition Scan (MUGA) is acceptable if ECHO is not available.

          -  ≥19 years of age

          -  Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to
             NCI CTCAE Version 4.03 Grade <1, in the opinion of the treating physician.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patient has a platelet count of <100,000/mm3, or absolute neutrophil count of
             <1500/mm3 or Hemoglobin <8.0gm/dL

          -  Patient has a calculated or measured creatinine clearance of <30 milliliters
             (mL)/minute

          -  Patient has total bilirubin >2 x upper limit of normal (ULN), or aspartate
             aminotransferase (AST), alanine aminotransferase (ALT) >3.5 x ULN

          -  Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Before study entry, any ECG
             abnormality at screening has to be documented by the investigator as not medically
             relevant.

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of: a) adequately treated basal cell carcinoma, squamous cell skin cancer,
             or thyroid cancer; b) carcinoma in situ of the breast; c) cancer considered cured by
             surgical resection or unlikely to impact survival during the duration of the study,
             such as localized transitional cell carcinoma of the bladder or benign tumors of the
             adrenal or pancreas.

          -  Known HIV, hepatitis B and hepatitis C infection

          -  Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to
             randomization

          -  Prior treatment with bortezomib

          -  Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             Carfilzomib)

          -  Has received prior radiation to >50% of the bone marrow

          -  Has had significant bleeding/thrombosis in previous 4 weeks

          -  Has received treatment with radiation therapy, surgery, chemotherapy, or an
             investigational agent within 4 weeks prior to registration, (6 weeks for radiation
             therapy, radionuclides, nitrosoureas, or Mitomycin C) or who have not recovered from
             adverse events due to agents administered more than 4 weeks earlier

          -  Has evidence of uncontrolled Central Nervous System (CNS) involvement (previous
             radiation and off steroids is acceptable)

          -  Patients may not be receiving any other investigational agents

          -  Has a serious uncontrolled intercurrent medical or psychiatric illness, including
             serious infection

          -  Is unable to comply with study requirements

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.