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High Doses of Vitamin C with Chemotherapy and Radiation Therapy in Treating Patients with Non-Small Cell Lung Cancer

Trial Status: Active

This phase II trial studies how well high doses of ascorbic acid (vitamin C) work in combination with chemotherapy and radiation therapy in patients with non-small cell lung cancer. High doses of intravenous vitamin C may change chemoradiation treatment effectiveness and / or tolerability. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Fractionated radiation therapy uses smaller doses of radiation therapy over time and may kill more tumor cells and have fewer side effects. Using high doses of vitamin C with chemotherapy and radiation therapy may work better in treating patients with non-small cell lung cancer.

Inclusion Criteria

  • Patients must have newly diagnosed histologically or cytologically confirmed non-small cell lung cancer (i.e., no prior biological therapy, immunotherapy, or chemotherapy)
  • Pleural effusions that are minimal (i.e. not visible on chest x-ray) that are too small to safely tap are eligible
  • Recommendation for carboplatin/paclitaxel with radiation therapeutic treatment
  • Must have baseline measurable or evaluable disease per RECIST (as per a diagnostic chest & abdomen computed tomography [CT] or a diagnostic chest CT scan with accompanying fludeoxyglucose F-18 [FDG] positron emission tomography [PET]/CT) identified within 60 days prior to consent
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 50%)
  • Platelets >= 100,000/mm^3 (=< 21days [d] of study day 1)
  • Creatinine < 1.5x institutional upper limits of normal (ULN) or creatinine clearance >= 60 mL/(min 1.73 m^2) for patients with elevated creatinine levels (=< 21d of study day 1)
  • Tolerate one test dose (15g) of ascorbate
  • Not pregnant. The effects of carboplatin and/or paclitaxel on the developing human fetus at the recommended therapeutic dose are unknown, however, therapeutic radiation is known to be teratogenic as well as abortifacient. Pregnancy tests will be obtained per institutional policies
  • Agree to acceptable birth control; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

  • Exudative pleural effusion, regardless of cytology
  • Recurrent non-small cell lung cancer
  • G6PD (glucose-6-phosphate dehydrogenase) deficiency
  • Patients actively receiving insulin are excluded unless approved by the investigational new drug (IND) medical monitor, IND sponsor, and the study principal investigator (PI)
  • Patients requiring daily finger-stick blood glucose measurements unless approved by the IND medical monitor, IND sponsor, and the study PI
  • Patients who are on warfarin and cannot have a drug substitution or who decline the drug substitution
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
  • Prior radiation therapy resulting in overlap of radiation therapy (RT) fields
  • Enrolled in another clinical trial with a targeted endpoint of treating the patient’s cancer (observational trials are acceptable)
  • 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
  • Lactating women
  • Known human immunodeficiency virus (HIV)-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 2 study

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE
Contact: Bryan G. Allen
Phone: 319-353-8836

PRIMARY OBJECTIVES:

I. Determine the efficacy of pharmacological ascorbic acid (ascorbate) combined with concurrent radiation therapy and chemotherapy (carboplatin/paclitaxel regimen) as measured by progression rate at completion of radiation and chemotherapy compared to historical controls for patients with inoperable locally advanced non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. Determine overall survival (OS) and progression free survival (PFS) of patients compared to historical controls.

II. Determine tumor response using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. Categorize and quantify adverse events compared to historical controls.

IV. Determine oxidative stress biomarkers in plasma during the course of treatment which will be compared to oxidative stress biomarkers obtained in a parallel study in subjects treated with radiation and carboplatin/paclitaxel.

OUTLINE:

Patients undergo radiation therapy 5 days per week, beginning within 28 days of signing the consent, for a total of 30 treatments. Concurrently, patients also receive paclitaxel intravenously (IV) over 60 minutes once a week followed by carboplatin IV over 30 minutes once a week for a total of 7 weeks, and an ascorbic acid infusion 3 times a week.

After completion of study treatment, patients are followed up at 4 weeks, 6 months, 12 months, and 2 years, and then periodically thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
Bryan G. Allen

  • Primary ID 201712770
  • Secondary IDs NCI-2018-00421
  • Clinicaltrials.gov ID NCT02905591