Pharmacological Ascorbate for Lung Cancer

April 16, 2024 updated by: Muhammad Furqan, Joseph J. Cullen, MD, FACS

A Phase II Trial of High-Dose Ascorbate in Stage IV Non-Small Cell Lung Cancer

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Holden Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ascorbate, paclitaxel, carboplatin
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
  • 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
Other Names:
  • Taxol
  • Nov-Onxol
  • Onxol
  • Paclitaxel Novaplus
Drug: Carboplatin
  • 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
Other Names:
  • Paraplatin
  • NovaPlus CARBOplatin
  • Amerinet Choice Carboplatin
  • Paraplatin NovaPlus
Drug: Ascorbic Acid
  • 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
Other Names:
  • Vitamin C
  • Ascorbate
  • Pharmacological ascorbate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Response
Time Frame: every 2 months for up to 5 years post treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Event Frequency
Time Frame: monthly for up to 6 months
Categorize and quantify using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4 from cycle 1 day 1 through 1 month post-infusion
monthly for up to 6 months
Progression Free Survival (PFS)
Time Frame: every 2 months for up to 5 years post treatment
The time (in months) it takes for disease to progress as defined by RECIST criteria. Timeframe will be from cycle 1, day 1 to date of progression.
every 2 months for up to 5 years post treatment
Overall Survival (OS)
Time Frame: every 2 months for up to 5 years post treatment
Time, measured in months, from cycle 1 day 1 until date of death from any cause
every 2 months for up to 5 years post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joseph J. Cullen, MD, FACS

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.

Investigators

  • Study Director: Joseph J. Cullen, MD, FACS, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

December 1, 2021

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

April 9, 2015

First Submitted That Met QC Criteria

April 14, 2015

First Posted (Estimated)

April 17, 2015

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201412760
  • 3P30CA086862 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared from those patient partners who agree to it. Data will be codified for the investigational team to provided additional details - as necessary - or confirm against source.

IPD Sharing Time Frame

After publication

IPD Sharing Access Criteria

Email the study chair or principal investigator; a non-disclosure and/or data usage agreement will most likely be required.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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