A Phase 2 Study Adding Ascorbate to Chemotherapy and Radiation Therapy for NSCLC

NCT ID: NCT02905591

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-16

Study Completion Date

2027-12-31

Brief Summary

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This clinical trial evaluates adding high-dose ascorbate (vitamin C) to a standard therapy for non-small cell lung cancer. The standard therapy is radiation therapy combined with carboplatin and paclitaxel (types of chemotherapy). All subjects will receive high-dose ascorbate in addition to the standard therapy.

Detailed Description

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For selected stages of non-small cell lung cancer (NSCLC), standard treatment involves radiation therapy and chemotherapy. The chemotherapy regimen typically used is paclitaxel and carboplatin. Both of these chemotherapeutic drugs are administered intravenously, using a vein in the arm. Radiation is administered using a machine external to the body (usually a linear accelerator). After combined therapy, NSCLC patients receive 2 extra cycles of chemotherapy, called "consolidation chemotherapy."

This study adds 75 grams of ascorbate (vitamin C, sometimes called pharmacological ascorbate because the dose is so high) at specific timepoints in the therapy. The ascorbate is administered intravenously - through a vein in your arm.

Participants will:

* receive 75 grams of intravenous ascorbate 3 times per calendar week while they are receiving radiation therapy. The IV will be running while the radiation therapy is administered.
* undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays.
* provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy

This active therapy portion lasts for about 10 to 12 weeks. After that is done, participants go back to standard follow-up for their cancer and any additional therapy their doctors believe they need.

However, it is very important the investigators remain in contact with participants; they will have life-long follow-up for this study.

Conditions

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Carcinoma, Non-Small-Cell Lung Non-Small Cell Lung Cancer Nonsmall Cell Lung Cancer Non-Small-Cell Lung Carcinoma NSCLC

Keywords

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pharmacological ascorbate ascorbic acid radiation chemotherapy carboplatin paclitaxel

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ChemoRT + Ascorbate

Radiation therapy, intravenous paclitaxel, intravenous carboplatin, intravenous ascorbic acid (pharmacological ascorbate)

Group Type EXPERIMENTAL

Radiation Therapy

Intervention Type DRUG

Conformal radiation administered daily, Monday through Friday Total dose is 60 Gray (Gy) and is delivered in 2 Gy fractions. One fraction is delivered daily for a total of 30 fractions in 30 days

Paclitaxel

Intervention Type DRUG

Administered intravenously (IV) Given the same day as carboplatin, but given before the carboplatin is administered

* the dose is 45 mg/m2 (standard dose)
* Administered weekly
* 6 to 7 weeks of therapy, depending on when radiation starts
* Standardized dose reductions are used

Carboplatin

Intervention Type DRUG

Administered intravenously (IV) GIven the same day as paclitaxel, immediately after the paclitaxel infusion is done.

* Prescribed at area-under-the-curve (AUC) = 2 using the Cockroft-Gault formula (standard)
* Administered weekly
* 6 to 7 weeks of therapy, depending on when radiation starts
* Standard dose reductions are used

Ascorbic Acid

Intervention Type DRUG

Administered intravenously

* 75 grams per infusion; each infusion is about 2 hours
* 3 infusion per calendar week
* The infusion is actively running for at least 20 minutes when radiation begins
* May be given while chemotherapy is delayed due to low counts
* Dose reductions are not used
* Given for 6 to 7 weeks, depending on when radiation starts

Interventions

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Radiation Therapy

Conformal radiation administered daily, Monday through Friday Total dose is 60 Gray (Gy) and is delivered in 2 Gy fractions. One fraction is delivered daily for a total of 30 fractions in 30 days

Intervention Type DRUG

Paclitaxel

Administered intravenously (IV) Given the same day as carboplatin, but given before the carboplatin is administered

* the dose is 45 mg/m2 (standard dose)
* Administered weekly
* 6 to 7 weeks of therapy, depending on when radiation starts
* Standardized dose reductions are used

Intervention Type DRUG

Carboplatin

Administered intravenously (IV) GIven the same day as paclitaxel, immediately after the paclitaxel infusion is done.

* Prescribed at area-under-the-curve (AUC) = 2 using the Cockroft-Gault formula (standard)
* Administered weekly
* 6 to 7 weeks of therapy, depending on when radiation starts
* Standard dose reductions are used

Intervention Type DRUG

Ascorbic Acid

Administered intravenously

* 75 grams per infusion; each infusion is about 2 hours
* 3 infusion per calendar week
* The infusion is actively running for at least 20 minutes when radiation begins
* May be given while chemotherapy is delayed due to low counts
* Dose reductions are not used
* Given for 6 to 7 weeks, depending on when radiation starts

Intervention Type DRUG

Other Intervention Names

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external beam radiation therapy (EBRT) intensity modulated radiation therapy (IMRT) Volumetric Arc Therapy (VMAT) XRT Nov-Onxol Onxol Paclitaxel Novaplus Taxol NovaPlus CARBOplatin Amerinet Choice Carboplatin Paraplatin Paraplatin NovaPlus Ascorbate Vitamin C Pharmacological ascorbate

Eligibility Criteria

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Inclusion Criteria

Note: patients who have a small pleural effusion that is too small to safety tap and is not visible on a chest x-ray are still eligible

* Pathologic diagnosis (i.e., cell sample, biopsy, tissue swap, bronchoscopy) of non-small cell lung cancer.
* Recommended to receive carboplatin \& paclitaxel with radiation therapy as a treatment
* Tumor or metastatic disease must measure at least 1 cm using a CT scan (CAT scan)
* Physician determined the patient is healthy enough for chemotherapy and radiation therapy
* At least part of the lung cancer must be viewable and measurable by CT or MRI
* A platelet count of at least 100,000 cells per mililiter
* A creatinine level of less than 1 1/2 times the upper limit of normal for the local lab test, or, a creatinine clearance of at least 60 mL/(min\*1.73m2)
* Not pregnant, and commit to using birth control during the study

Exclusion Criteria

* Exudative pleural effusion
* Recurrent non-small cell lung cancer
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Patients actively receiving insulin or patients whose doctors have recommended current insulin use
* Patients requiring daily finger-stick blood glucose measurements
* Patients who are on the following drugs and cannot have a substitution or who decline the substitution:

* warfarin
* flecainide
* methadone
* amphetamines
* quinidine
* chlorpropamide
* Prior radiation therapy that would result in a field overlap
* Enrolled in another therapeutic clinical trial
* Uncontrolled, intercurrent illness
* Lactating women
* HIV positive individuals undergoing therapy due to known drug:drug interaction between antiretroviral drugs and high-dose ascorbate therapy

If all the above are met, the potential participant will receive a 15 gram challenge dose of ascorbate via intravenous infusion. This is the final screening procedure.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Holden Comprehensive Cancer Center

OTHER

Sponsor Role collaborator

Joseph J. Cullen, MD, FACS

OTHER

Sponsor Role lead

Responsible Party

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Bryan Allen

Assistant Professor, Department of Radiation Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Joseph J Cullen, MD, FACS

Role: STUDY_DIRECTOR

University of Iowa

Locations

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Holden Comprehensive Cancer Cener

Iowa City, Iowa, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 28366679 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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201712770

Identifier Type: -

Identifier Source: org_study_id

3P30CA086862

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U01CA140206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1P01CA217797-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link