lung cancer lung carcinoma
Conditions
Interventions
12 patients with lymph node negative early stage (T1c-3N0-2) NSCLC (stage
IA3-IIB, UICC8th edition) will be included. Patients will be discussed in the
multidisciplinary tumor board (MTB). All subje
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed NSCLC 2. T1c-3N0-2, here T3 tumors are based on size, but not based in invasion into the thoracic wall, mediastinum, vertebra or diaphragm or ipsilateral lung nodules 3. Willing and able to provide written informed consent for the trial 4. Above 18 years of age on day of signing informed consent 5. Have measurable disease based on RECIST 1.1. [18] 6. Have a ECOG performance status of 0-1, and are considered operable based on pulmonary function test and/or exercise testing 7. Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of immunotherapy: a. Leukocytes >= 3,000/mm3 b. Absolute neutrophil count (ANC) >= 1000/mm3 c. Platelet count >= 75,000/mm3 d. Hemoglobin >= 6 mmol/L (9.7 g/dL) e. Creatinine =40 mL/min (if using the Cockcroft-Gault formula below): i. Female CrCl = [(140 - age) x weight x 0.85]/(0.85 x creat in mmol/L) ii. Male CrCl = [(140 - age) x weight x 1.00]/(0.81 x creat in mmol/L) f. Total Bilirubin 30 kg 9. Must have a life expectancy of at least 12 weeks
Exclusion criteria
Exclusion criteria: 1. Prior surgery and/or radiotherapy on the ipsilateral thorax 2. Patients deemed inoperable 3. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 4. Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 5. 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) 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 6. Uncontrolled intercurrent illness, including but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 7. Active infection requiring systemic therapy. 8. A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 9. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 10. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 11. Has received prior therapy with an anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 12. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pathological response will be defined in terms of percentage of patients with a MPR and a pathologic complete response (pCR). Pathologic tumor response will be assessed upon resection of the tumor. Viable tumor cell percentages will be assessed. Pathologic complete response is defined as 0% viable tumor cells, MPR is defined as less than 10% residual viable tumor cells. 2. Safety will be measured as the percentage of patients with adverse events. The severity of adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The following post-operative complications will be registered: air leakage >5 days, infection (empyema, wound), fistula formation. Any study medication related complication leading to delay or canceling of the routine surgery procedures will be registered. | — |
Secondary
| Measure | Time frame |
|---|---|
| • to assess tumor immune infiltration after durva and RT, • to assess radiologic and metabolic response to durva and RT | — |
Countries
Netherlands
Outcome results
None listed