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Docetaxel With or Without Ascorbic Acid in Treating Patients With Metastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02516670
Recruitment Status : Recruiting
First Posted : August 6, 2015
Last Update Posted : July 21, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE August 4, 2015
First Posted Date  ICMJE August 6, 2015
Last Update Posted Date July 21, 2020
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2015)
  • Occurrence of a >= 50% decline in PSA [ Time Frame: From baseline to up to 24 weeks ]
    Analyzed using a one-sided 0.05 alpha level Fisher's exact test.
  • Proportions of worst grade adverse events among those specified (fatigue, nausea, bone pain, and anorexia) in the categories: no toxicities, grade 1-2, and grade 3-4 in the two arms of the study [ Time Frame: Up to 30 days after the last dose of study drug ]
    Analyzed using a one-sided 0.10 Cochran-Armitage test for trend.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2015)
  • Docetaxel dose reductions [ Time Frame: Up to 24 weeks ]
    The number of dose reductions and total number of completed cycles will be summarized by study arm.
  • Proportions of maximum grade SAE of all types [ Time Frame: Up to 30 days after last dose of study drug ]
    Compared using the Cochran-Armitage test for trend.
  • Proportions of patients experiencing grade 3 or higher (maximum grade) serious adverse events (SAE) of fatigue, nausea, bone pain, and/or anorexia [ Time Frame: Up to 24 weeks ]
    Compared between arms of the study with the Cochran-Armitage test for trend.
  • Quality of life (QoL) as measured by the FACT-P questionnaire [ Time Frame: Up to course 6 of therapy (18 weeks) ]
    FACT-P scores will be compared at cycle 4 and 6 between arms of the study with an analysis of covariance using the baseline QoL score as a covariate.
  • Radiographic progression free survival (rPFS) [ Time Frame: Up to 3 years ]
    For each treatment arm, the median rPFS and a 2-sided 95% confidence interval will be provided. Estimates of the time-to-event curves from the Kaplan-Meier method will be provided and compared using the log-rank statistic.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 4, 2015)
  • Effect of ascorbic acid on docetaxel exposure [ Time Frame: Up to 24 weeks ]
    To determine whether ascorbic acid alters docetaxel exposure and compare between treatment arms, pharmacokinetics samples will be collected prior to, during, and after ascorbic acid and docetaxel infusions.
  • F2-isoprostanes, a pharmacodynamic measure of oxidant injury in vivo [ Time Frame: Up to course 6 (18 weeks) ]
    Correlative analyses will assess the association between ascorbic acid and lipid peroxidation (F2-isoprostanes) in the two study arms, globally, and over time. Comparisons of ascorbic acid and F2-isoprostanes by study arm at cycle 1, cycle 2, cycle 4 and cycle 6, accounting for baseline measures obtained from the same patient, will be made by taking differences between post baseline and baseline values and comparing these differences between arms of the study with t-tests. Regression will also be used to assess the association between F2-isoprostane and ascorbic acid at cycle 4 and at cycle 6.
  • Peak and trough ascorbic acid levels [ Time Frame: Up to 24 weeks ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Docetaxel With or Without Ascorbic Acid in Treating Patients With Metastatic Prostate Cancer
Official Title  ICMJE A Randomized Phase 2 Trial of Ascorbic Acid in Combination With Docetaxel in Men With Metastatic Prostate Cancer
Brief 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.
Detailed Description

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.

TERTIARY OBJECTIVES:

I. To determine whether ascorbic acid alters docetaxel exposure and compare between treatment arms.

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 thrice weekly. 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 over 60 minutes thrice weekly. 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 for 30 days and then every 6 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Hormone-Resistant Prostate Cancer
  • Metastatic Prostate Carcinoma
  • Stage IV Prostate Cancer
Intervention  ICMJE
  • Dietary Supplement: Ascorbic Acid
    Given IV
    Other Names:
    • 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one
    • Asorbicap
    • C Vitamin
    • C-Long
    • Ce-Vi-Sol
    • Cecon
    • Cenolate
    • Cetane
    • Cevalin
    • L-Ascorbic Acid
    • VIT C
    • Vitamin C
    • Vitamin-C
  • Drug: Docetaxel
    Given IV
    Other Names:
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Other: Placebo
    Given IV
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE
  • Experimental: Arm A (docetaxel, ascorbic acid)
    Patients receive docetaxel IV on day 1 and ascorbic acid IV twice weekly. The first ascorbic acid treatment will be given on day 1 (same day as docetaxel). Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Dietary Supplement: Ascorbic Acid
    • Drug: Docetaxel
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Other: Quality-of-Life Assessment
  • Placebo Comparator: Arm B (docetaxel, placebo)
    Patients receive docetaxel IV on day 1 and placebo IV twice weekly.The first placebo treatment will be given on day 1 (same day as docetaxel). Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Docetaxel
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Other: Placebo
    • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2015)
69
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2030
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Channing Paller, MD 410-955-8804 cpaller1@jhmi.edu
Contact: Elisabeth Prophet 410-955-6655 eprophe1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02516670
Other Study ID Numbers  ICMJE J15106
NCI-2015-01169 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB00070691 ( Other Identifier: JHM IRB )
J15106 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center )
P30CA006973 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Channing Paller, MD Johns Hopkins University/Sidney Kimmel Cancer Center
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP