Dual-immunotherapy and short-course medium-dose radiotherapy, followed by surgery for tumor microenvironment modification in early-stage NSCLC
- Conditions
- lung cancerlung carcinoma1003866610006436
- Registration Number
- NL-OMON52295
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 12
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 <= 1.5 x ULN or creatinine clearance (CrCl) >=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 <= 1.5 x ULN (except subjects with Gilbert Syndrome)
g. AST and ALT <= 2.5 times the upper limit of normal
h. Subjects must have adequate lung function to permit surgical resection
determined by pre-enrollment pulmonary function tests to include DLCO
8. Body weight >30 kg
9. Must have a life expectancy of at least 12 weeks
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Pathological response will be defined in terms of percentage of patients<br /><br>with a MPR and a pathologic complete response (pCR). Pathologic tumor response<br /><br>will be assessed upon resection of the tumor. Viable tumor cell percentages<br /><br>will be assessed. Pathologic complete response is defined as 0% viable tumor<br /><br>cells, MPR is defined as less than 10% residual viable tumor cells.<br /><br>2. Safety will be measured as the percentage of patients with adverse events.<br /><br>The severity of adverse events will be graded using the National Cancer<br /><br>Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.<br /><br>The following post-operative complications will be registered: air leakage >5<br /><br>days, infection (empyema, wound), fistula formation. Any study medication<br /><br>related complication leading to delay or canceling of the routine surgery<br /><br>procedures will be registered.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• to assess tumor immune infiltration after durva and RT,<br /><br>• to assess radiologic and metabolic response to durva and RT</p><br>