Assessing the Immunomodulatory Effects of Pharmacologic Ascorbate with Durvalumab (MEDI 4736) in Non-Small Cell Lung Cancer: a Window of Opportunity 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
• 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).