Docetaxel with or without Ascorbic Acid in Treating Patients with Metastatic Prostate Cancer

Status: Active

Description

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-naive 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 >= 60 mL/minute [Cockcroft-Gault])
  • Men of reproductive potential and those who are surgically sterilized (i.e., post vasectomy) 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 warfarin anticoagulation therapy
  • 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 known active uncontrolled hepatitis B, or hepatitis C infection

Locations & Contacts

District of Columbia

Washington
Sibley Memorial Hospital
Status: Active
Contact: Channing J. Paller
Phone: 410-955-8239
Email: cpaller1@jhmi.edu

Maryland

Annapolis
Anne Arundel Medical Center
Status: Active
Contact: Jason David Taksey
Phone: 443-481-4884
Email: jtaksey@aahs.org
Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Channing J. Paller
Phone: 410-955-8239
Email: cpaller1@jhmi.edu

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Contact: Elisabeth Iljas Heath
Phone: 313-576-8715
Email: heathe@karmanos.org

Ohio

Cleveland
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Status: Active
Contact: Christopher James Hoimes
Phone: 216-844-5946
Email: christopher.hoimes@uhhospitals.org
Westlake
UH Seidman Cancer Center at Saint John Medical Center
Status: Active
Contact: Christopher James Hoimes
Phone: 216-844-5946
Email: Christopher.hoimes@UHhospitals.org

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: William Kevin Kelly
Phone: 215-503-4490
Email: William.Kelly@jefferson.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare the proportion of metastatic prostate cancer patients with a prostate specific antigen (PSA) decline of >= 50% over 8 cycles of docetaxel with ascorbic acid (Arm A) versus docetaxel with placebo (Arm B).

II. To compare the proportion of adverse events (fatigue, nausea, bone pain, and anorexia) experienced by metastatic prostate cancer patients receiving either docetaxel with ascorbic acid (Arm A) versus docetaxel with placebo (Arm B).

SECONDARY OBJECTIVES:

I. To assess radiographic progression free survival (rPFS) in patients with metastatic prostate cancer and compare between treatment arms.

II. To assess the proportion of high grade serious adverse events (fatigue, nausea, bone pain, and anorexia) in patients with metastatic prostate cancer and compare between treatment arms during 8 cycles of treatment.

III. To assess the proportion of high grade serious adverse events (all types) in patients with metastatic prostate cancer and compare between treatment arms during 8 cycles of treatment.

IV. To assess changes in quality of life measures as assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.

V. To assess the proportion of metastatic prostate cancer patients requiring docetaxel dose reductions and compare between treatment arms during 8 cycles of treatment.

VI. To assess overall survival (OS) in patients with metastatic prostate cancer and compare between treatment arms.

EXPLORATORY OBJECTIVES:

I. To determine whether ascorbic acid alters docetaxel exposure and compare between treatment arms. To correlate docetaxel exposure with clinical outcomes.

II. To determine peak and trough ascorbic acid levels.

III. As a pharmacodynamic measure of oxidant injury in vivo, measure F2-isoprostanes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive docetaxel intravenously (IV) over 60 minutes on day 1 and ascorbic acid IV 2 times per week. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive docetaxel IV over 60 minutes on day 1 and placebo IV 2 times per week. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Channing J. Paller

Trial IDs

Primary ID J15106
Secondary IDs NCI-2015-01169, CRMS-61984, IRB00070691
Clinicaltrials.gov ID NCT02516670