Vitamin C with Chemotherapy and Radiation for Lung Cancer

(XACT-LUNG Trial)

Overseen By Muhammad Furqan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph J. Cullen, MD, FACS

Must be taking: Carboplatin, Paclitaxel

Must not be taking: Warfarin, Flecainide

Disqualifiers: Recurrent cancer, G6PD deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

Duration: 10-12 weeks

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide unless a substitution is possible. If you are on these medications and cannot switch, you may not be eligible to participate.

What data supports the effectiveness of the treatment involving Vitamin C with Chemotherapy and Radiation for Lung Cancer?

Research shows that combining paclitaxel and carboplatin with radiation therapy can improve local and systemic control of non-small cell lung cancer, potentially increasing survival rates. This combination has been found to be relatively safe and more active compared to some standard treatments. ^{1 2 3 4 5}

Is the combination of Vitamin C, chemotherapy, and radiation therapy safe for lung cancer treatment?

The combination of paclitaxel and carboplatin with radiation therapy has been found to be relatively safe and well-tolerated in patients with advanced non-small cell lung cancer, with manageable side effects. ^{1 2 3 5 6}

What makes the treatment of Vitamin C with chemotherapy and radiation for lung cancer unique?

This treatment is unique because it combines Vitamin C with standard chemotherapy drugs (carboplatin and paclitaxel) and radiation therapy, potentially enhancing the effectiveness of the chemotherapy and radiation by acting as a radiosensitizer, which may improve local and systemic control of the cancer. ^{1 2 3 4 5}

Research Team

Joseph J Cullen, MD, FACS

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults with non-small cell lung cancer who are healthy enough for chemotherapy and radiation, have a measurable tumor of at least 1 cm by CT or MRI, and not pregnant. They must have normal platelet counts and kidney function, no severe pleural effusion, no G6PD deficiency, not on certain medications like warfarin or insulin, and not HIV positive on antiretroviral therapy.

Inclusion Criteria

My kidney function tests are within the required range.

I have a small fluid collection in my chest that can't be safely removed and isn't seen on an X-ray.

The tumor or cancer spread needs to be at least 1 cm in size as seen on a CT scan.

Exclusion Criteria

Enrolled in another therapeutic clinical trial

I am taking one of the specified drugs and cannot or will not switch to a different one.

I have fluid buildup in the lining of my lungs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose ascorbate with standard chemotherapy and radiation therapy

10-12 weeks

3 visits per week (in-person)

Consolidation Chemotherapy

Participants receive 2 extra cycles of chemotherapy after combined therapy

6-8 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months (in-person)

Long-term Follow-up

Participants have life-long follow-up for the study

Up to 20 years

Every 6 months (in-person)

Treatment Details

Interventions

• Ascorbic Acid
• Carboplatin
• Paclitaxel
• Radiation Therapy

Trial Overview The study tests adding high-dose vitamin C (ascorbate) to the standard treatment regimen of carboplatin and paclitaxel chemotherapy combined with radiation therapy. All participants will receive this additional ascorbate alongside their prescribed treatments.

Participant Groups

Group I: ChemoRT + Ascorbate Experimental Treatment 4 Interventions

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

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Joseph J. Cullen, MD, FACS

Lead Sponsor

Trials

4

Recruited

110+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

Findings from Research

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

A systematic review of 31 studies involving 3090 patients treated with cisplatin-etoposide and 48 studies with 3728 patients treated with carboplatin-paclitaxel showed that both chemotherapy regimens had similar efficacy in treating unresectable stage III non-small-cell lung cancer, with no significant differences in overall survival or progression-free survival.

However, carboplatin-paclitaxel was associated with fewer severe hematological toxic effects compared to cisplatin-etoposide, making it a safer option for patients undergoing concurrent thoracic radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review. Steuer, CE., Behera, M., Ernani, V., et al.[2022]

The combination of paclitaxel and carboplatin followed by thoracic radiation therapy (TRT) has shown promising efficacy in treating locally advanced non-small-cell lung cancer (NSCLC), with a 60% partial response rate to combined therapy and a median survival of 15.3 months for all patients.

The treatment was well-tolerated, with manageable side effects, and the chemotherapy doses were safely escalated, indicating that this approach can be an effective option for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. Movsas, B., Hudes, RS., Schol, J., et al.[2019]

References

1. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. [2019]