Vitamin C + Durvalumab for Lung Cancer

Overseen By Muhammad Furqan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Muhammad Furqan

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 4-9 weeks

36 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using immunosuppressive medication or receiving certain treatments like chemotherapy or radiotherapy for cancer. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Durvalumab for lung cancer?

Research shows that Durvalumab significantly improves progression-free survival and overall survival in patients with stage III non-small cell lung cancer when used after chemoradiotherapy. This has been demonstrated in both clinical trials and real-world studies. ^{1 2 3 4 5}

Is the combination of Vitamin C and Durvalumab safe for treating lung cancer?

Durvalumab has been shown to be generally safe in patients with non-small cell lung cancer, but it can increase the risk of immune-related side effects like pneumonitis (lung inflammation). Safety data for Vitamin C in combination with Durvalumab specifically is not available, but Vitamin C is generally considered safe for most people. ^{3 4 6 7 8}

What makes the drug Durvalumab unique for lung cancer treatment?

Durvalumab is unique because it is an immunotherapy drug that targets the PD-L1 protein, helping the immune system attack cancer cells, and is particularly effective in patients with high PD-L1 expression. It is used after chemoradiotherapy in stage III non-small-cell lung cancer, offering a new option for patients who have not progressed after initial treatment. ^{3 4 9 10 11}

What is the purpose of this trial?

This is a descriptive, proof of concept, open-label, randomized, 3-arm, window of opportunity trial to evaluate the immunomodulatory role of pharmacological ascorbate with Durvalumab

Research Team

Muhammad Furqan

Principal Investigator

University of Iowa

Eligibility Criteria

Adults over 18 with confirmed non-small cell lung cancer that's surgically removable and hasn't spread, who are in good health with proper organ function. They must expect to live at least 12 weeks, weigh over 30 kg, and have no history of severe allergies or other cancers. Women of childbearing age must use effective contraception.

Inclusion Criteria

I am fully active or can carry out light work.

I agree to use effective birth control during and 90 days after the study.

I am a woman not currently pregnant, either post-menopausal or have had surgery to prevent pregnancy.

Exclusion Criteria

Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment Arm assignment.

Participation in another clinical study with an investigational product during the last 4 weeks prior to randomization

Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Durvalumab alone, Durvalumab plus ascorbate, or no neoadjuvant therapy before surgical resection

4-9 weeks

Durvalumab every 3 weeks, Ascorbate three times a week

Surgical Resection

Surgical removal of the tumor is performed

1 week

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

Up to three years

Treatment Details

Interventions

• Durvalumab
• Pharmacological ascorbate
• Surgery

Trial Overview The trial is testing the combination of a high-dose vitamin C (pharmacological ascorbate) with Durvalumab immunotherapy against standard surgery for early-stage lung cancer. It aims to see if this mix can better modulate the immune system to fight cancer.

Participant Groups

Group I: Durvalumab as monotherapy Experimental Treatment 1 Intervention

Two cycles of Durvalumab 1500 mg every 3 weeks, as monotherapy

Group II: Combination of pharmacological ascorbate plus Durvalumab Experimental Treatment 2 Interventions

Combination of pharmacological ascorbate 75 grams intravenously three times a week x 4 weeks plus Durvalumab 1500 mg every 3 weeks for two cycles

Group III: Control (no neoadjuvant therapy) Active Control 1 Intervention

Serve as control and patients will not receive any neoadjuvant therapy before going to surgery. Once randomize, they can go to surgery without any delays.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Muhammad Furqan

Lead Sponsor

Trials

5

Recruited

130+

Findings from Research

In a study of 1006 patients with stage III non-small cell lung cancer (NSCLC), early discontinuation of adjuvant durvalumab therapy was common, primarily due to tumor progression and immune-related adverse events, highlighting the need for careful monitoring during treatment.

The analysis indicated that shorter durations of durvalumab (6 or 9 months) may provide similar progression-free survival compared to the full 12-month course, suggesting that optimizing treatment duration could balance efficacy and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. Bryant, AK., Sankar, K., Zhao, L., et al.[2023]

The AEGEAN trial is a phase III study involving approximately 800 patients with resectable, early-stage non-small-cell lung cancer (NSCLC) that aims to evaluate the effectiveness of durvalumab combined with chemotherapy before surgery and as a monotherapy after surgery.

This study will assess key outcomes such as pathological complete response and event-free survival, potentially improving treatment strategies for patients with Stage II-III NSCLC, where current survival rates remain low despite standard postoperative chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial. Heymach, JV., Mitsudomi, T., Harpole, D., et al.[2022]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a study of 1006 veterans with stage III non-small cell lung cancer (NSCLC), the addition of durvalumab after chemoradiotherapy significantly improved progression-free survival (PFS) and overall survival (OS), with hazard ratios of 0.62 and 0.57 respectively, indicating a strong benefit from the treatment.

While durvalumab improved OS in veterans compared to those who received only chemoradiotherapy, their survival rates were still lower than those observed in the PACIFIC clinical trial population, suggesting that real-world outcomes may differ from clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer. Sankar, K., Bryant, AK., Strohbehn, GW., et al.[2022]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

In a multicenter study of 35 patients with unresectable stage III non-small cell lung cancer and baseline Grade 1 radiation pneumonitis, durvalumab was found to be a feasible treatment option, with 85% of patients experiencing no severe adverse events after 3 months.

Only 15% of patients experienced Grade ≥3 adverse events, and 20% had disease progression, indicating that durvalumab has a manageable safety profile in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis following concurrent chemoradiotherapy: a multicenter prospective cohort study. Sugimoto, T., Fujimoto, D., Sato, Y., et al.[2022]

In a study of 35 patients with unresectable stage III non-small cell lung cancer (NSCLC) and baseline grade 1 radiation pneumonitis, durvalumab showed promising safety and effectiveness, with a median progression-free survival of 11.4 months.

Despite some patients experiencing increased pneumonitis, including 31% with grade ≥2 pneumonitis, durvalumab treatment was generally well-tolerated, suggesting it can be a viable option for this patient population after chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective multicenter cohort study of durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis. Sugimoto, T., Fujimoto, D., Sato, Y., et al.[2022]

In a phase 3 trial involving 713 patients with stage III unresectable non-small-cell lung cancer, durvalumab significantly improved overall survival compared to placebo, with a 24-month survival rate of 66.3% versus 55.6%.

Durvalumab also prolonged progression-free survival, with a median duration of 17.2 months compared to 5.6 months for placebo, and no new safety concerns were identified, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In a study of 126 patients with unresectable stage III non-small-cell lung cancer, 56% were eligible for durvalumab after chemoradiotherapy, and those who were ineligible had significantly shorter progression-free survival (9.7 months vs. 18.4 months) and overall survival (26.4 months vs. 58.7 months).

The research indicates that durvalumab is safe and beneficial for a considerable number of patients who do not meet the eligibility criteria of the PACIFIC trial, suggesting that its use could be expanded beyond the trial's limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. Boys, E., Gao, B., Hui, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. [2023]

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

Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer. [2022]

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

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

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

Durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis following concurrent chemoradiotherapy: a multicenter prospective cohort study. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Prospective multicenter cohort study of durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis. [2022]

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

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

11. Singapore pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. [2023]