Accelerated Hypofractionated or Conventionally Fractionated Radiotherapy and Durvalumab in Treating Patients with Stage II-III Non-small Cell Lung Cancer
18 Years and older, Male and Female
This phase I trial studies how well giving accelerated hypofractionated (ACRT) or conventionally fractionated radiation therapy and durvalumab works in treating patients with stage II-III non-small cell lung cancer. Accelerated hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventionally fractionated radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body’s immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving accelerated hypofractionated radiation therapy or conventionally fractionated radiation therapy with durvalumab will work better in treating patients with non-small cell lung cancer.
I. To evaluate if the addition of MEDI4736 (durvalumab) to two schedules of radiation therapies (60 Gy in 30 fractions or 60 Gy in 15 fractions) is safe.
I. To examine if the addition of MEDI4736 (durvalumab) to radiation therapy is feasible.
II. To assess toxicities associated with the addition of MEDI4736 (durvalumab) to radiation therapy.
III. To obtain preliminary estimates of progression-free survival (PFS), using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, in patients who received MEDI4736 (durvalumab) added to radiation.
I. To assess the impact the addition of MEDI4736 (durvalumab) has on progression-free survival, using immune-related response criteria (irRC) guidelines.
II. To assess the changes in circulating tumor cells (CTCs) and various immune parameters during treatment with durvalumab and radiotherapy and changes after completion of treatment.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 starting 2 weeks prior to radiation therapy. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo accelerated hypofractionated radiation therapy (ACRT) 1 fraction per day, 5 days per week for 15 fractions.
ARM II: Patients receive durvalumab as in Arm I. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4 months for 1 year.
- Pathologic (cytological or histological) proof of diagnosis of stage II-III (American Joint Committee on Cancer [AJCC] 8th edition [ed.]) unresectable or inoperable, non-metastatic non-small cell lung cancer (NSCLC) within 60 days prior to registration, with no liver or renal end organ damage, as determined by normal laboratory values noted below. Locally recurrent, N1-N3 disease following surgery without prior radiation therapy is eligible. Patients with N1 to N3 and undetectable primary lung tumors (T0) are eligible
- Pathological diagnosis of PD-L1 high expressing tumors (>= 50%) within 60 days prior to registration (using Dako 22C3 immunohistochemistry [IHC] antibody or the Ventana SP263 antibody platforms) performed at a Clinical Laboratory Improvement Act (CLIA)-certified lab
- Appropriate stage for study entry based on the following diagnostic workup:
* History/physical examination within 30 days prior to registration;
* Positron emission tomography (PET)/computed tomography (CT) scan for staging within 30 days prior to registration (note: if CT portion of PET/CT scan is not of diagnostic quality, then a separate CT scan with contrast is required);
* Magnetic resonance imaging (MRI) scan of the brain with contrast; if medically contraindicated, then CT scan of the brain with contrast (unless medically contraindicated) is acceptable, within 30 days prior to registration;
* Sufficient lung function with forced expiratory volume in 1 second (FEV1) >= 0.8 liter or >= 35% predicted and carbon monoxide diffusing capability (DLCO) >= 40% with or without bronchodilator within 30 days prior to registration;
* Patients who meet the criterion above without oxygen (O2), but who need acute (started within 10 days prior to registration) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable
- Body weight > 30 kg
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
- Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 30 days prior to registration)
- Lymphocyte count >= 500 cells/mm^3 (within 30 days prior to registration)
- Platelet count >= 100,000 cells/mm^3 (within 30 days prior to registration)
- Hemoglobin >= 9.0 g/dL (within 30 days prior to registration) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
- Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 (within 30 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) with the following exception (within 30 days prior to registration):
* Patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days prior to registration)
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients, obtained within 14 days prior to registration. 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 < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
- Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
* They must have a CD4 count of greater than 250 cells/mcL
* They must not be receiving prophylactic therapy for an opportunistic infection
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Treatment Sites in Georgia
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