Non-small Cell Lung Cancer
Conditions
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
Detailed description
Participants in this research study have stage I Non-Small Cell Lung Cancer (NSCLC) that was found to be suitable for surgery as a first line treatment. The usual treatment for this disease is to remove the tumor with surgery, and then evaluate after surgery if other additional treatments such as chemotherapy or targeted therapy are needed. The purpose of this research study is to compare three different ways of treating stage 1 NSCLC, to see if adding treatment before surgery can reduce the chance of the tumor recurring after surgical removal. In this study, patients will be randomly assigned to one of three treatments: * Durvalumab followed by surgical resection of the tumor. * Durvalumab plus ascorbate (also known as vitamin C), followed by surgical resection of the tumor. * Surgical resection alone. No therapy prior to surgery. This is the same as standard care (SOC) for this disease.
Interventions
DRUGDurvalumab
Given intravenous (IV) infusion as monotherapy or in combination with pharmacological ascorbate
Given intravenously in combination with Durvalumab
PROCEDURESurgery (SOC)
Surgery SOC
Sponsors
William Zeitler
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: Creatinine CL (mL/min)= Weight (kg) x (140 - Age) divided by 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min)= Weight (kg) x (140 - Age) x 0.85 divided by 72 x serum creatinine (mg/dL) * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Must have a life expectancy of at least 12 weeks * Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from the time of screening, throughout the total duration of the drug treatment, and during the 90-day post-drug washout period. * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women 1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CD8+ T cells 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. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) and adverse events (AEs) per CTCAE v5 | Throughout the treatment period, 4 weeks | Assess safety and tolerability of the combination of Pharmacological Ascorbate and Durvalumab in the neoadjuvant setting (Arm:2) |
| Pathologic Complete Response (pCR) rate | Up to three years following completion of treatment | The proportion of patients with a pathologic complete response, defined as no viable tumor. |
| Major Pathologic Response (MPR) rate | Up to three years following completion of treatment | The proportion of patients with a major pathologic response, defined as residual viable tumor of 10% or less. |
| Event-Free Survival | Up to three years following completion of treatment | Time from randomization to progression of disease that precludes surgery, local or distant recurrence, or death due to any cause. |
| Overall Survival | Up to three years following completion of treatment | Time from randomization to death due to any cause. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWilliam Zeitler, MD, MPH
University of Iowa
Outcome results
None listed