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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Phase 2 Trial of Ascorbic Acid in Combination With Docetaxel in Men With Metastatic Prostate Cancer

Conditions
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Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: Ascorbic Acid
* Drug: Docetaxel
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study
* Other: Placebo
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (docetaxel, ascorbic acid)<br>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. | Dietary Supplement: Ascorbic Acid<br>* Given IV<br>* Other names: Vitamin-C;Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Placebo Comparator: Arm B (docetaxel, placebo)<br>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. | Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Other: Placebo<br>* Given IV<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participates With a Decline in Prostate-specific Antigen From Their Baseline Measurement | prostate-specific antigen decline will be defined as ≥ 50% from baseline measurement | up to 24 weeks | 
| Number of Participants With Adverse Events | Number of participants experiencing fatigue, nausea, bone pain, and anorexia as defined by CTCAE 4.0 | Up to 30 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Number of Times Docetaxel Had Dose Reductions | The number of dose reductions and total number of completed cycles will be summarized by study arm. | Up to 24 weeks | 
| Number of Serious Adverse Events | 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 event | Up to 30 days after last dose of study drug | 
| Number of Participates Experiencing Serious Adverse Events (SAE) | 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 | Up to 24 weeks | 
| Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire | 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. | Up to course 6 of therapy (18 weeks) | 
| Radiographic Progression Free Survival (rPFS) | To determine the rPFS of participates that receive at least one dose of ascorbic acid compared to those who received placebo | Up to 3 years |