Pharmacological Ascorbate for Lung Cancer

NCT02420314 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2014127603P30CA086862
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Ascorbate; Ascorbic acid; Vitamin C; NSCLC; Non Small Cell Lung Cancer; carboplatin; paclitaxel

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  From cycle 1, day 1, to documented disease progression in CT imaging as described by RECIST criteria

  every 2 months for up to 5 years post treatment

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  every 2 months for up to 5 years post treatment

• Overall Survival (OS)

  every 2 months for up to 5 years post treatment

Study Arms (1)

Ascorbate, paclitaxel, carboplatin

EXPERIMENTAL

Paclitaxel, administered once per cycle (3 weeks) Carboplatin, administered once per cycle (3 weeks) Pharmacological ascorbate (ascorbic acid) infusions, 2 times per week for 3 weeks

Drug: Paclitaxel; Drug: Carboplatin; Drug: Ascorbic Acid

Interventions

Paclitaxel DRUG

* Administered intravenously (IV) * Prescribed at 200 mg/m2 (standard dose) * Given once every 21 days (i.e., one cycle) * Up to 4 cycles are administered depending on disease response

Also known as: Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol

Ascorbate, paclitaxel, carboplatin

Carboplatin DRUG

* Administered intravenously (IV) * Prescribed at AUC = 6 using the Cockcroft-Gault formula (standard dose) * Given once every 21 days (i.e., one cycle) * Up to 4 cycles are administered depending on disease response

Also known as: Amerinet Choice Carboplatin, NovaPlus CARBOplatin, Paraplatin, Paraplatin NovaPlus

Ascorbate, paclitaxel, carboplatin

Ascorbic Acid DRUG

* Administered intravenously (IV) * 75g per infusion * Two infusions per week * 1 cycle is 3 weeks * given up to 4 cycles * may be given while chemotherapy if delayed due to low counts

Also known as: Pharmacological ascorbate, Vitamin C, Ascorbate

Ascorbate, paclitaxel, carboplatin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• % 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

Sponsors & Collaborators

• Joseph J. Cullen, MD, FACS: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator
• Holden Comprehensive Cancer Center: collaborator
• McGuff Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• 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.

  PMID: 28366679 RESULT

• 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.

  PMID: 35525024 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Taxes; Carboplatin; Ascorbic Acid

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Coordination Complexes; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Limitations and Caveats

Single arm, open label trial increases bias and reduces internal validity.

Results Point of Contact

• Title: Dr. Muhammad Furqan
• Organization: University of Iowa

muhammad-furqan@uiowa.edu

319-356-1616

Study Officials

• Joseph J. Cullen, MD, FACS

  University of Iowa

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 9, 2015
• First Posted: April 17, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2021
• Study Completion: August 27, 2022
• Last Updated: August 20, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication
• Access Criteria: Email the study chair or principal investigator; a non-disclosure and/or data usage agreement will most likely be required.

Locations

US (1)