Clinical Trials /

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

NCT02516670

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Docetaxel With or Without Ascorbic Acid in Treating Patients With Metastatic Prostate Cancer
  • Official Title: A Randomized Phase 2 Trial of Ascorbic Acid in Combination With Docetaxel in Men With Metastatic Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: J15106
  • SECONDARY ID: NCI-2015-01169
  • SECONDARY ID: IRB00070691
  • SECONDARY ID: J15106
  • SECONDARY ID: P30CA006973
  • NCT ID: NCT02516670

Conditions

  • Hormone-Resistant Prostate Cancer
  • Metastatic Prostate Carcinoma
  • Stage IV Prostate Cancer

Interventions

DrugSynonymsArms
DocetaxelRP56976, Taxotere, Taxotere Injection ConcentrateArm A (docetaxel, ascorbic acid)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (docetaxel, ascorbic acid)ExperimentalPatients 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.
  • Docetaxel
Arm B (docetaxel, placebo)Placebo ComparatorPatients 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.
  • Docetaxel

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),
             hepatitis B, or hepatitis C infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of a >= 50% decline in PSA
Time Frame:From baseline to up to 24 weeks
Safety Issue:
Description:Analyzed using a one-sided 0.05 alpha level Fisher's exact test.

Secondary Outcome Measures

Measure:Docetaxel dose reductions
Time Frame:Up to 24 weeks
Safety Issue:
Description:The number of dose reductions and total number of completed cycles will be summarized by study arm.
Measure:Proportions of maximum grade SAE of all types
Time Frame:Up to 30 days after last dose of study drug
Safety Issue:
Description:Compared using the Cochran-Armitage test for trend.
Measure: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
Safety Issue:
Description:Compared between arms of the study with the Cochran-Armitage test for trend.
Measure:Quality of life (QoL) as measured by the FACT-P questionnaire
Time Frame:Up to course 6 of therapy (18 weeks)
Safety Issue:
Description: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.
Measure:Radiographic progression free survival (rPFS)
Time Frame:Up to 3 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

January 15, 2019