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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well a combination of high-dose Vitamin C and the drug Durvalumab (an immunotherapy) can help the immune system fight non-small cell lung cancer before surgery. Participants will be divided into three groups: one will receive both treatments, another will receive only Durvalumab, and the last group will undergo surgery without any pre-treatment. Suitable candidates have non-small cell lung cancer that is surgically removable, with tumors larger than 1 cm but no larger than 4 cm. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Durvalumab, a drug used to treat various cancers, is generally safe. Patients with solid tumors, such as lung cancer, usually tolerate it well. However, some patients might experience side effects where the drug causes the immune system to mistakenly attack healthy cells.

When combined with high-dose Vitamin C administered through an IV, the safety results are encouraging. Although less information exists about this specific combination, each component has demonstrated safety in different studies. For any concerns, discussing them with the healthcare team involved in the trial is always best. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for lung cancer, which often include chemotherapy and radiation, the investigational treatment combining pharmacological ascorbate (high-dose Vitamin C) with Durvalumab offers a unique approach. Pharmacological ascorbate is believed to enhance the immune response and may improve the effectiveness of Durvalumab, an immunotherapy drug that works by blocking a protein called PD-L1. This combination could potentially boost the body's ability to fight cancer cells more effectively. Researchers are excited because this approach might lead to improved outcomes with fewer side effects compared to conventional treatments. Additionally, using Vitamin C in high doses intravenously is a novel method that could provide a new angle in enhancing cancer treatment efficacy.

What evidence suggests that this trial's treatments could be effective for lung cancer?

In this trial, some participants will receive Durvalumab as monotherapy. Previous studies have shown promising results for non-small cell lung cancer. Specifically, patients who took Durvalumab experienced longer periods without cancer progression compared to those who did not. Another group in this trial will receive a combination of high doses of Vitamin C through an IV with Durvalumab. Research suggests that this combination might enhance the immune system's ability to fight cancer and has been linked to better outcomes in some patients. Although more research is needed, these findings offer hope that this treatment could be effective for lung cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

William Zeitler, MD, MPH

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

William Zeitler

Lead Sponsor

Published Research Related to This Trial

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]

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 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 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 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 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 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]

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 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]

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]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00556-8/fulltext

215TiP A phase II study of durvalumab (MEDI 4736) ... DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

A phase II study of durvalumab (MEDI4736) immediately ... Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709937

Durvalumab after Chemoradiotherapy in Stage III Non– ... The 12-month progression-free survival rate was 55.9% (95% CI, 51.0 to 60.4) with durvalumab and 35.3% (95% CI, 29.0 to 41.7) with placebo, and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02352948

NCT02352948 | A Global Study to Assess the Effects ... This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.9029

Safety and clinical activity of durvalumab (MEDI4736), an ... Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)53877-7/fulltext

Safety and efficacy of durvalumab (MEDI4736) plus ... Similar safety results were reported with this combination in an ongoing study of Japanese patients with advanced solid tumors (NCT02141347)1. 1. Takahashi Y et ...