Clinical trial NCT02420314: Pharmacological Ascorbate for Lung Cancer
Official title: A Phase II Trial of High-Dose Ascorbate in Stage IV Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Ascorbate
Ascorbic acid
Vitamin C
NSCLC
Non Small Cell Lung Cancer
carboplatin
paclitaxel
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
name: Holden Comprehensive Cancer Center
name: McGuff Pharmaceuticals, Inc.
First posted: 2015-04-17
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of non-small cell lung cancer (NSCLC) in adults. All subjects will receive high-dose ascorbate in addition to the standard treatment.

Detailed description: Standard treatment for non-small cell lung cancer (NSCLC) involves a combined therapy of paclitaxel and carboplatin. These drugs are administered once every 21 days. This study adds high dose ascorbic acid (75g per infusion) twice per week for up to 4 cycles of therapy.

Participants will:

* receive high doses of intravenous (IV) ascorbate two times a week during each 3 week chemotherapy.
* have blood samples drawn to measure blood ascorbate levels once every 21 days
* have blood samples drawn to measure iron and ferritin levels before treatment, then on cycles 1 and 3.

The active therapy portion of this study lasts for 4 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.

Eligibility criteria: Inclusion Criteria:

* newly diagnosed stage IIIB or IV non -small cell lung cancer. The potential participant must not have received first-line cytotoxic therapy. Prior use of first-line EGFR inhibitors or ALK inhibitors is allowed if there was progression on therapy.
* CNS metastasis is allowed if the metastasis is treated and there are no signs of progression following treatment. The potential participant must be off steroids for at least 3 days and be stable.
* At least 18 years of age
* ECOG performance status of 0, 1, or 2
* absolute neutrophil count (ANC) of at least 1500 cells per mm³
* platelet count of at least 100,000 cells per mm³
* hemoglobin of at least 8 g/dL
* creatinine within 1.5 times the upper limit of normal
* total bilirubin within 1.5 times the upper limit of normal
* ALT within 3 times the institutional upper limit of normal
* AST within 3 times the institutional upper limit of normal
* the participant must tolerate a 15g ascorbate test infusion (screening dose)
* patients who received prior treatment with curative intent must have experienced a treatment-free interval of at least 6 months since the last treatment
* the participant must not be pregnant, be willing to have a pregnancy test done if deemed necessary, and be willing to use adequate birth control during the study
* not breastfeeding
* independently able to provide consent (legally authorized representative and/or power of attorney is not allowed)

Exclusion Criteria:

* known sensitizing EGFR mutations or ALK gene rearrangements if the participant has not yet tried EGFR or ALK inhibitor therapies. If the potential participant's biopsy did not allow for gene analysis (inconclusive, not enough tissue), the patient is considered eligible for the study. Enrollment on this clinical trial after progression on targeted therapy is allowed
* 50% or greater PD-L1 expression (patients with unknown PD-L1 expression or when PD-L1 expression can't be determined due to insufficient tumor sample or other reasons remain eligible)
* receiving warfarin therapy and cannot tolerate drug substitution
* active hemoptysis within 1 week of screening (more than 1/2 teaspoon of blood per day)
* actively receiving insulin at the time of ascorbate infusion
* G6PD deficiency
* leptomeningeal disease
* potential participants cannot be on the following drugs: flecainide, methadone, amphetamines, quinidine, or chlorpropamide.
* known active invasive malignancy other than the lung cancer under therapy (non-melanoma skin cancer or carcinoma in situ of the cervix or bladder are exempted)
* potential participants may not enroll in, or be actively receiving treatment from, a therapeutic clinical trial for their cancer. Observational studies (including imaging studies) are acceptable.
* uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements
* known HIV positive individuals cannot be enrolled in this trial because high-dose ascorbate is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral agents

Primary outcomes:
measure: Tumor Response
timeFrame: every 2 months for up to 5 years post treatment
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: every 2 months for up to 5 years post treatment
measure: Overall Survival (OS)
timeFrame: every 2 months for up to 5 years post treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: University of Iowa
name: Joseph J. Cullen, MD, FACS
role: STUDY_DIRECTOR
References:
citation: Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30.
citation: Furqan M, Abu-Hejleh T, Stephens LM, Hartwig SM, Mott SL, Pulliam CF, Petronek M, Henrich JB, Fath MA, Houtman JC, Varga SM, Bodeker KL, Bossler AD, Bellizzi AM, Zhang J, Monga V, Mani H, Ivanovic M, Smith BJ, Byrne MM, Zeitler W, Wagner BA, Buettner GR, Cullen JJ, Buatti JM, Spitz DR, Allen BG. Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer. Redox Biol. 2022 Jul;53:102318. doi: 10.1016/j.redox.2022.102318. Epub 2022 Apr 20.