locally advanced non-small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non-small cell lung cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Ipilimumab
Pharmaceutical Form: Concentrate and solvent for solution for injection/infusion
Trade Name: nivolumab
Pharmaceutical Form:
Sponsors
Amsterdam UMC, VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed NSCLC, a histological biopsy is mandatory 2. T3-4, N0-1 tumors based on size or upon ingrowth into the thoracic wall, mediastinum, vertebra or diaphragm 3. Patients that are irresectable upfront, but expected to be resectable after chemoradiotherapy induction, as per multidisciplinary tumor board evaluation 4. Be willing and able to provide written informed consent for the trial. 5. Be above 18 years of age on day of signing informed consent. 6. Have measurable disease based on RECIST 1.1. 9. 7. Have a performance status of 0-1 on the ECOG Performance Scale. 8. Demonstrate adequate organ function. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: 1. Known oncogenic drivers such as activating EGFR or BRAF mutations or ALK or ROS1 gene rearrangements 2. Prior surgery and/or radiotherapy on the ipsilateral thorax 3. Patients deemed inoperable 4. 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. 5. 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. 6. Active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids. 7. Evidence of interstitial lung disease or active, non-infectious pneumonitis. 8. Active infection requiring systemic therapy. 9. Ahistory of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 10. Active Hepatitis B or C. 11. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 13. 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. A Woman of Childbearing Potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab. These durations have been calculated using the upper limit of the half-life for nivolumab (~25 days) and are based on the recommendation that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days after the last dose of nivolumab. Females should not breastfeed while receiving nivolumab and for any subsequent protocol-specified period. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. Local laws and regulations may require use of alternative and/or additional contraception methods. One of the highly effective methods of contraception listed below is required during study duration and until the end of relevant sys
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the safety and feasibility of adding ipilimumab-nivolumab to a CRT induction protocol •To assess the efficacy of adding ipilimumab-nivolumab to CRT on the likelihood of a pCR and MPR ;Secondary Objective: •Local and distant recurrence rates, disease free survival (DFS) •Overall survival (OS) at 1 and 2 years ;Primary end point(s): Safety defined as (i) the percentage of patients with adverse events (NCI CTCAE), and with each adverse event, the grade and the relationship to ipi/nivo will be assessed, and (ii) complications that lead to delays in administering CRT, or to cancellation of surgery, as well as the rates of post-surgical morbidity. Pathologic complete responses, as well as the percentage of viable tumor in other cases, will be assessed on all the resection specimens. ;Timepoint(s) of evaluation of this end point: during the study and finally after finishing inclusion and follow up of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical outcome parameters such as time to local or distant recurrence, and OS at 1 and 2 years will be registered. ;Timepoint(s) of evaluation of this end point: during the study and finally after finishing inclusion and follow up of the study | — |
Countries
Netherlands
Contacts
Public ContactIdris Bahce
Amsterdam UMC, VU University Medical Center
Outcome results
None listed