Clinical trial NCT02516670: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hormone-Resistant Prostate Cancer
Metastatic Prostate Carcinoma
Stage IV Prostate Cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-08-06
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)
* Have a know active uncontrolled hepatitis B, or hepatitis C infection

Primary outcomes:
measure: Number of Participates With a Decline in Prostate-specific Antigen From Their Baseline Measurement
timeFrame: up to 24 weeks
measure: Number of Participants With Adverse Events
timeFrame: Up to 30 days after the last dose of study drug
Secondary outcomes:
measure: Average Number of Times Docetaxel Had Dose Reductions
timeFrame: Up to 24 weeks
measure: Number of Serious Adverse Events
timeFrame: Up to 30 days after last dose of study drug
measure: Number of Participates Experiencing Serious Adverse Events (SAE)
timeFrame: Up to 24 weeks
measure: Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire
timeFrame: Up to course 6 of therapy (18 weeks)
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: Up to 3 years
Other outcomes:
measure: Effect of Ascorbic Acid on Docetaxel Exposure
timeFrame: Up to 24 weeks
measure: F2-isoprostanes, a Pharmacodynamic Measure of Oxidant Injury in Vivo
timeFrame: Up to course 6 (18 weeks)
measure: Peak and Trough Ascorbic Acid Levels
timeFrame: Up to 24 weeks
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Annapolis
country: United States
facility: Anne Arundel Health System, Research Institute
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Seidman Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Johns Hopkins University/Sidney Kimmel Cancer Center
name: Channing Paller, MD
role: PRINCIPAL_INVESTIGATOR
References: