Docetaxel With or Without Ascorbic Acid in Treating Patients With Metastatic Prostate Cancer
- Conditions
- Hormone-Resistant Prostate CancerMetastatic Prostate CarcinomaStage IV Prostate Cancer
- Interventions
- Dietary Supplement: Ascorbic AcidOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: PlaceboOther: Quality-of-Life Assessment
- Registration Number
- NCT02516670
- 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
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 50
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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
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Have a pathological diagnosis of prostate carcinoma
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Patients may be receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone < 50 ng/dL
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Patient may be receiving bone targeted agents
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Have evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or Prostate Cancer Working Group 2 (PCWG2) criteria
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Have ECOG performance status 0-1
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Have an estimated life expectancy > 4 months
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Absolute neutrophil count >= 1500/mm^3
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Platelets >= 100,000/mm^3
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Hemoglobin >= 9 g/dL
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Total bilirubin =< 1.0 upper limit of normal (ULN)
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Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
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Creatinine =< 1.6 mg/dl (for patients with > 1.6 mg/dl, calculated or measured creatinine clearance must be >= 55 mL/minute [Cockcroft-Gault])
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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
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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
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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
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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)
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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
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Have had palliative radiation or biological cancer therapy within 2 weeks prior to the first dose of study drug
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Have received other investigational drugs within 28 days prior to enrollment
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Is expected to require any other form of systemic or localized antineoplastic therapy while on study
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Patients who require frequent (several times a day) monitoring of their blood glucose or patients who have recently been hospitalized for glucose control
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Are being treated with anticoagulation therapy (aspirin and nonsteroidal anti-inflammatory drugs [NSAIDS] are allowed)
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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
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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
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Has glucose-6-phosphate dehydrogenase (G6PD) deficiency
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Have end stage renal disease
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Has history of calcium oxalate stones
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Has history of iron overload
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Have a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
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Have a know active uncontrolled hepatitis B, or hepatitis C infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (docetaxel, ascorbic acid) Laboratory Biomarker Analysis 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. Arm A (docetaxel, ascorbic acid) Pharmacological Study 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. Arm B (docetaxel, placebo) Docetaxel 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. Arm A (docetaxel, ascorbic acid) 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. Arm A (docetaxel, ascorbic acid) Docetaxel 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. Arm B (docetaxel, placebo) Laboratory Biomarker Analysis 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. Arm B (docetaxel, placebo) 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. Arm A (docetaxel, ascorbic acid) Quality-of-Life Assessment 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. Arm B (docetaxel, placebo) Pharmacological Study 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. Arm B (docetaxel, placebo) Quality-of-Life Assessment 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events Up to 30 days after the last dose of study drug Number of participants experiencing fatigue, nausea, bone pain, and anorexia as defined by CTCAE 4.0
Number of Participates With a Decline in Prostate-specific Antigen From Their Baseline Measurement up to 24 weeks prostate-specific antigen decline will be defined as ≥ 50% from baseline measurement
- Secondary Outcome Measures
Name Time Method Number of Serious Adverse Events Up to 30 days after last dose of study drug Number of serious adverse events of all types as defined by Common Terminology Criteria for Adverse Events 4.0.
A serious adverse event is an undesirable sign, symptom, or medical condition that:
* Results in death
* Is life threatening
* Requires inpatient hospitalization or causes prolongation of existing hospitalization for \>24 hours
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Is an important medical eventRadiographic Progression Free Survival (rPFS) Up to 3 years To determine the rPFS of participates that receive at least one dose of ascorbic acid compared to those who received placebo
Average Number of Times Docetaxel Had Dose Reductions Up to 24 weeks The number of dose reductions and total number of completed cycles will be summarized by study arm.
Number of Participates Experiencing Serious Adverse Events (SAE) Up to 24 weeks Number of serious adverse events defined as grade 3 or higher (fatigue, nausea, bone pain, and anorexia) in participates as defined by CTCAE 4.0
Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire Up to course 6 of therapy (18 weeks) The (FACT-P) is made up of 39 question, with the total score ranging between 0 and 156 with 0 being the best and 156 as the worst.
Trial Locations
- Locations (6)
Anne Arundel Health System, Research Institute
🇺🇸Annapolis, Maryland, United States
University Hospitals of Cleveland Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States