Docetaxel With or Without Ascorbic Acid in Treating Patients With Metastatic Prostate Cancer
Condition: Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Ascorbic Acid; Docetaxel; Laboratory Biomarker Analysis; Pharmacological Study; Placebo; Quality-of-Life Assessment
Intervention description: Given IV; Given IV; Correlative studies; Correlative studies; Given IV; Ancillary studies
Intervention MeSH terms: Vitamins; Ascorbic Acid; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 50.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well docetaxel works when given with or without
      ascorbic acid in treating patients with prostate cancer that has spread to other places in
      the body. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Ascorbic acid (vitamin C) is a water-soluble vitamin that may
      help inhibit the growth of cancer cells. It is not yet known whether docetaxel works better
      when given with or without ascorbic acid in treating prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have metastatic castration-resistant prostate cancer (prostate cancer progressing
             despite castrate levels of testosterone [< 50 ng/dL] using standard measures of
             progression defined by Prostate Cancer Working Group 2), are chemo-naïve for
             metastatic castration-resistant prostate cancer (mCRPC); patients must have
             symptomatic disease or visceral metastases or otherwise be eligible for docetaxel
             treatment per investigator judgment (e.g. for progression on imaging or rapidly rising
             PSA despite 2nd line hormonal treatment);

               -  Note: Six cycles of prior docetaxel are allowed in hormone-sensitive disease, per
                  Eastern Cooperative Oncology Group (ECOG) 3805 data and have been off of
                  docetaxel for at least 12 months

          -  Have a pathological diagnosis of prostate carcinoma

          -  Patients may be receiving continuous hormonal ablation with surgical or medical
             castration with baseline testosterone < 50 ng/dL

          -  Patient may be receiving bone targeted agents

          -  Have evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
             and/or Prostate Cancer Working Group 2 (PCWG2) criteria

          -  Have ECOG performance status 0-1

          -  Have an estimated life expectancy > 4 months

          -  Absolute neutrophil count >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< 1.0 upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x ULN

          -  Creatinine =< 1.6 mg/dl (for patients with > 1.6 mg/dl, calculated or measured
             creatinine clearance must be >= 55 mL/minute [Cockcroft-Gault])

          -  Men of reproductive potential and those who are surgically sterilized (i.e.,
             postvasectomy) must agree to practice effective barrier contraception that has an
             expected failure rate of < 1% during and for 30 days after discontinuation of study
             treatment

               -  If condoms are used as a barrier contraceptive, a spermicidal agent should be
                  added to ensure that pregnancy does not occur

          -  Have the ability to understand, and have given 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

        Exclusion Criteria:

          -  Have had known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for CNS involvement for at least one week prior to trial treatment; patients
             with primary brain tumors are not eligible; however, as patients are completing
             abiraterone therapy, they will be allowed to continue up to 10 mg/day of prednisone

          -  Have had prior chemotherapy for metastatic disease in castration-resistant prostate
             cancer (prior chemotherapy for hormone-sensitive disease, more than twelve months
             prior to registration, is acceptable)

          -  Have had had surgery within four weeks of dosing of investigational agent, excluding
             minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary
             stent placement

          -  Have had palliative radiation or biological cancer therapy within 2 weeks prior to the
             first dose of study drug

          -  Have received other investigational drugs within 28 days prior to enrollment

          -  Is expected to require any other form of systemic or localized antineoplastic therapy
             while on study

          -  Patients who require frequent (several times a day) monitoring of their blood glucose
             or patients who have recently been hospitalized for glucose control

          -  Are being treated with anticoagulation therapy (aspirin and nonsteroidal
             anti-inflammatory drugs [NSAIDS] are allowed)

          -  The subject requires concomitant treatment with the following inhibitors of cytochrome
             P450, family 3, subfamily A, polypeptide 4 (CYP3A4):

               -  Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin

               -  Antifungals: itraconzaole, ketoconazole, voriconazole, fluconazole, posaconazole

               -  Antidepressants: nefazodone

               -  Antidiuretic: conivaptan

               -  Anti-retrovirals: delaviridine or protease inhibitors (ritonavir, indinavir,
                  lopinavir/ritonavir, saquinavir, nelfinavir) or cobicistat-boosted
                  antiretrovirals

               -  Gastrointestinal (GI): cimetidine, aprepitant

               -  Hepatitis C: boceprevir, telaprevir

               -  Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos,
                  star fruit, exotic citrus fruits, or grapefruit hybrids

          -  Have 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

          -  Has glucose-6-phosphate dehydrogenase (G6PD) deficiency

          -  Have end stage renal disease

          -  Has history of calcium oxalate stones

          -  Has history of iron overload

          -  Have a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Have a know active uncontrolled hepatitis B, or hepatitis C infection