Ascorbate With Durvalumab in Non-Small Cell Lung Cancer (NSCLC)

NCT06083454 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 202303162
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• CD8+ T cells quantified as the percentage of lymphocytes that are CD8+ T cells

  Determine if Pharmacological Ascorbate and durvalumab can potentiate or enhance an immune response in the NSCLC tumor-microenvironment compared to durvalumab alone. This will be evaluated in the surgically resected specimens of patients after receiving neoadjuvant therapy. CD8+ T cells will be quantified as the percentage of lymphocytes that are CD8+ T cells

  Following surgical resection which will be performed during weeks 5-9 from the day of randomization.

Secondary Outcomes (5)

• Incidence of dose limiting toxicities (DLTs) and adverse events (AEs) per CTCAE v5

  Throughout the treatment period, 4 weeks

• Pathologic Complete Response (pCR) rate

  Up to three years following completion of treatment

• Major Pathologic Response (MPR) rate

  Up to three years following completion of treatment

• Event-Free Survival

  Up to three years following completion of treatment

• Overall Survival

  Up to three years following completion of treatment

Study Arms (3)

Durvalumab as monotherapy

EXPERIMENTAL

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

Drug: Durvalumab

Combination of pharmacological ascorbate plus Durvalumab

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Pharmacological ascorbate

Control (no neoadjuvant therapy)

ACTIVE COMPARATOR

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.

Procedure: Surgery (SOC)

Interventions

Durvalumab DRUG

Given intravenous (IV) infusion as monotherapy or in combination with pharmacological ascorbate

Combination of pharmacological ascorbate plus Durvalumab; Durvalumab as monotherapy

Pharmacological ascorbate DRUG

Given intravenously in combination with Durvalumab

Combination of pharmacological ascorbate plus Durvalumab

Surgery (SOC) PROCEDURE

Surgery SOC

Control (no neoadjuvant therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Age \> 18 years at time of study entry regardless of gender or ethnic/racial background.
• Histologically or cytologically confirmed non-small cell lung cancer
• Clinical stage I with tumor size \>1 cm to 4 cm (either T1b or T1c or T2a and N0 M0) according to American Joint Committee on Cancer 8th edition
• Surgically resectable with adequate lung functions to undergo surgery as determined by thoracic surgeon.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal.
• Measured creatinine clearance (CL) ≥50 mL/min or Calculated creatinine CL≥50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks prior to randomization
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Prior systemic therapy for early-stage NSCLC that is under consideration for thisstudy.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) clinically stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
• Patients with celiac disease controlled by diet alone

Sponsors & Collaborators

• William Zeitler: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• William Zeitler, MD, MPH

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: 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. Translational and clinical findings of this study can then be applied more broadly to design and address clinically oriented questions in various NSCLC treatment settings.

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 16, 2023
• Study Start: October 23, 2023
• Primary Completion: April 4, 2025
• Study Completion: January 9, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)