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

Information source: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer

Intervention: Ascorbic Acid (Dietary Supplement); Docetaxel (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Placebo (Other); Quality-of-Life Assessment (Other)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Sidney Kimmel Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Channing Paller, Principal Investigator, Affiliation: Johns Hopkins University/Sidney Kimmel Cancer Center

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Occurrence of a >= 50% decline in PSA

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

Secondary outcome:

Docetaxel dose reductions

Proportions of maximum grade SAE of all types

Proportions of patients experiencing grade 3 or higher (maximum grade) serious adverse events (SAE) of fatigue, nausea, bone pain, and/or anorexia

Quality of life (QoL) as measured by the FACT-P questionnaire

Radiographic progression free survival (rPFS)

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

Locations and Contacts

Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland 21287, United States; Not yet recruiting
Channing J. Paller, Phone: 410-955-8239, Email: cpaller1@jhmi.edu
Channing J. Paller, Principal Investigator
Additional Information

Starting date: January 2016
Last updated: August 4, 2015

Page last updated: August 23, 2015

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