Non-Small Cell Lung Cancer
Conditions
Interventions
During the feasibility phase of the trial in the first cohort, cohort 1A, 6
patients will be treated with one course of Durvalumab 1500mg plus Tremelimumab
75mg via IV infusion followed by one 2nd c
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written and dated informed consent prior to any study specific procedures. 2. Male or female aged 18 years or older. 3. WHO performance status of 0 or 1. 4. Pathologically proven NSCLC stage III or inoperable stage II (cT1-3N0-1), according to the 8th edition of the AJCC staging, with a clinical indication for concurrent chemo-irradiation. 5. Body weight >30kg 6. Patients with locoregional recurrent lung tumour following surgery or a second primary cancer are eligible, unless a pneumonectomy was performed. 7. Negative pregnancy test (urine or serum) for female patients with childbearing potential; 8. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of =12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of =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). 9. Adequate organ function. Minimum required laboratory data: see protocol 10. All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 11. Patients should be medically operably defined by: a. Sufficient cardiopulmonary function (Brunelli, Kim, Berger, & Addrizzo-Harris, 2013) b. No major contra-indications for surgery.
Exclusion criteria
Exclusion criteria: Exclusion Criteria A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Patients with grade 3 dyspnoea or worse at baseline (according to CTCAE version 4.03). 2. Prior radiotherapy to the thorax. 3. Participation in another clinical study with an investigational product during the last 4 weeks. 4. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study. 5. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of chemotherapy. 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, 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., Exclusion Criteria 7. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow*up schedule; those conditions should be discussed with the patient before registration in the trial. 8. Any condition that, in the opinion of the investigator, would interfere with evaluation of the CRT or interpretation of patient safety or study results. 9. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Durvalumab or Tremelimumab may be included only after consultation with the Study Physician. 10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone 11. Subject noncompliance that, in the opinion of the investigator or sponsor, warrants withdrawal; eg, refusal to adhere to scheduled visits 12. General contra-indications for immunotherapy: a. 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, or human immunodeficiency virus (positive HIV 1/2 antibodies). 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. Pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is safety. Treatment is deemed safe if adverse events can be managed and patients have completed the planned multimodality treatment, defined by CIT-CRT/R. | — |
Secondary
| Measure | Time frame |
|---|---|
| The main secondary endpoint is the percentage of patients with mediastinal and / or radiological down-staging following CIT-induction allowing a complete resection. The other secondary endpoints include: • Efficacy endpoints - 1-Year disease control rate (DCR) - Disease free survival (DFS) - Overall survival (OS) - Pathological complete response • Safety endpoints: - The rate of grade 3-4 and 5 treatment-related adverse events that occur during CIT-CRT/R. - The rate of grade 3-4 and 5 treatment-related adverse events that occur during maintenance treatment and 3-month follow-up. - The rate of immune-related adverse events during treatment • Translational research endpoints: - Correlation FDG-uptake with pathological response and inflammation. - Pathology - Development of a measure of assess the pathological response - Immunology - Descriptive analysis of the development of a tumour-specific T-cell response - Description of regional v.s. local immune response - Early predictors of response - Breath analyses: - Predictive of response to combined modality immunotherapy at baseline - Early response prediction | — |
Countries
Netherlands
Outcome results
None listed