Carcinoma, Non-Small-Cell LungPhase 2NCT02420314
Pharmacological Ascorbate for Lung Cancer
A Phase 2 study testing Paclitaxel, Carboplatin and Ascorbic Acid in people with Carcinoma, Non-Small-Cell Lung, run by Joseph J. Cullen, MD, FACS at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Paclitaxel, Carboplatin and Ascorbic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 27 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: 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.
Read the 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.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Paclitaxel, Carboplatin, Ascorbic Acid
- Keywords
- Ascorbate, Ascorbic acid, Vitamin C, NSCLC, Non Small Cell Lung Cancer, carboplatin, paclitaxel
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol
- 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
CarboplatinDrug
Also called Amerinet Choice Carboplatin, NovaPlus CARBOplatin, Paraplatin, Paraplatin NovaPlus
- 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
Ascorbic AcidDrug
Also called Pharmacological ascorbate, Vitamin C, Ascorbate
- 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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Ascorbic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
From cycle 1, day 1, to documented disease progression in CT imaging as described by RECIST criteria
Measured: every 2 months for up to 5 years post treatment
Secondary outcomes (2)
Progression Free Survival (PFS)
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.
Measured: every 2 months for up to 5 years post treatment
Overall Survival (OS)
Time, measured in months, from cycle 1 day 1 until date of death from any cause
Measured: every 2 months for up to 5 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2021
- Study completion27 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph J. Cullen, MD, FACS
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institutes of Health (NIH), Holden Comprehensive Cancer Center, McGuff Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Muhammad Furqan, University of Iowa
- Investigators
- Joseph J. Cullen, MD, FACS, Study director, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420314
- Sponsor's protocol ID
- 201412760
- Other IDs
- 3P30CA086862
- Status last verified
- Jul 2024
- First submitted
- 9 Apr 2015
- Last updated
- 20 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 28366679Furqan 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.
PubMed 35525024
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of High-Dose Ascorbate in Stage IV Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02420314
- Acronym / sponsor ID
- 201412760
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Ascorbate, Ascorbic acid, Vitamin C, NSCLC, Non Small Cell Lung Cancer, carboplatin, paclitaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Joseph J. Cullen, MD, FACSUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institutes of Health (NIH), Holden Comprehensive Cancer Center, McGuff Pharmaceuticals, Inc.
- Study start
- Apr 2015 (actual)
- Primary completion
- Dec 2021 (actual)
- Study completion
- 27 Aug 2022 (actual)
- First posted
- 17 Apr 2015 (estimated)
- Results
- Posted 17 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ascorbate, paclitaxel, carboplatin | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: Ascorbic AcidPaclitaxel, 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaclitaxelAlso: Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol* 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 | Drug | Ascorbate, paclitaxel, carboplatin |
| CarboplatinAlso: Amerinet Choice Carboplatin, NovaPlus CARBOplatin, Paraplatin, Paraplatin NovaPlus* 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 | Drug | Ascorbate, paclitaxel, carboplatin |
| Ascorbic AcidAlso: Pharmacological ascorbate, Vitamin C, Ascorbate* 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 | Drug | Ascorbate, paclitaxel, carboplatin |
Primary outcome
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
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28366679Schoenfeld 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.
- Results publication: PubMed 35525024Furqan 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph J. Cullen, MD, FACS study director
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel, Carboplatin and Ascorbic Acid in people with Carcinoma, Non-Small-Cell Lung, run by Joseph J. Cullen, MD, FACS at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Response (time frame: every 2 months for up to 5 years post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02420314, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024; AzTrials last refreshed its copy on 2 Nov 2026.