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



Status:Recruiting
Conditions:Prostate Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:1/19/2019
Start Date:June 2016
End Date:January 2030
Contact:Channing Paller, MD
Email:cpaller1@jhmi.edu
Phone:410-955-8804

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

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.

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.

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
We found this trial at
6
sites
11100 Euclid Avenue
Cleveland, Ohio 44106
Phone: 216-844-5946
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4100 John R
Detroit, Michigan 48201
800-527-6266
Phone: 313-576-8715
Barbara Ann Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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Annapolis, Maryland 21401
Phone: 443-481-4884
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401 North Broadway
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Channing J. Paller
Phone: 410-955-8804
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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1020 Walnut St
Philadelphia, Pennsylvania 19107
(215) 955-6000
Phone: 215-503-4490
Thomas Jefferson University We are dedicated to the health sciences and committed to educating professionals,...
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5255 Loughboro Rd NW
Washington, District of Columbia 20016
(202) 537-4000
Phone: 202-660-6500
Sibley Memorial Hospital Sibley Memorial Hospital, in Northwest Washington, D.C., has a distinguished history of...
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