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

NCT02516670 | Terminated Phase 2 Results DMC

• 4 other identifiers: J15106NCI-2015-01169IRB00070691P30CA006973
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

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.

Conditions

Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Average Number of Times Docetaxel Had Dose Reductions

  Up to 24 weeks

• Number of Serious Adverse Events

  Up to 30 days after last dose of study drug

• Number of Participates Experiencing Serious Adverse Events (SAE)

  Up to 24 weeks

• Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire

  Up to course 6 of therapy (18 weeks)

• Radiographic Progression Free Survival (rPFS)

  Up to 3 years

Other Outcomes (3)

• Effect of Ascorbic Acid on Docetaxel Exposure

  Up to 24 weeks

• F2-isoprostanes, a Pharmacodynamic Measure of Oxidant Injury in Vivo

  Up to course 6 (18 weeks)

• Peak and Trough Ascorbic Acid Levels

  Up to 24 weeks

Study Arms (2)

Arm A (docetaxel, ascorbic acid)

EXPERIMENTAL

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; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment

Arm B (docetaxel, placebo)

PLACEBO COMPARATOR

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; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Other: Quality-of-Life Assessment

Interventions

Ascorbic Acid DIETARY_SUPPLEMENT

Given IV

Also known as: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long, Ce-Vi-Sol, Cecon, Cenolate, Cetane, Cevalin, L-Ascorbic Acid, VIT C, Vitamin C, Vitamin-C

Arm A (docetaxel, ascorbic acid)

Docetaxel DRUG

Given IV

Also known as: RP56976, Taxotere, Taxotere Injection Concentrate

Arm A (docetaxel, ascorbic acid); Arm B (docetaxel, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (docetaxel, ascorbic acid); Arm B (docetaxel, placebo)

Pharmacological Study OTHER

Correlative studies

Arm A (docetaxel, ascorbic acid); Arm B (docetaxel, placebo)

Placebo OTHER

Given IV

Also known as: placebo therapy, PLCB, sham therapy

Arm B (docetaxel, placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (docetaxel, ascorbic acid); Arm B (docetaxel, placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Anne Arundel Health System, Research Institute

Annapolis, Maryland, 21401, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University Hospitals of Cleveland Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Paller CJ, Zahurak ML, Mandl A, Metri NA, Lalji A, Heath E, Kelly WK, Hoimes C, Barata P, Taksey J, Garrison DA, Patra K, Milne GL, Anders NM, Nauroth JM, Durham JN, Marshall CH, Markowski MC, Eisenberger MA, Antonarakis ES, Carducci MA, Denmeade SR, Levine M. High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial. Cancer Res Commun. 2024 Aug 1;4(8):2174-2182. doi: 10.1158/2767-9764.CRC-24-0225.

  PMID: 39076107 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ascorbic Acid; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Channing Paller Associate Professor Urologic Oncology
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

cpaller1@jhmi.edu

4109558239

Study Officials

• Channing Paller, MD

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 6, 2015
• Study Start: June 20, 2016
• Primary Completion: July 31, 2021
• Study Completion: October 14, 2021
• Last Updated: June 7, 2023
• Results First Posted: August 8, 2022

Record last verified: 2023-06

Locations

US (6)