Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

This Phase 1 trial aimed to determine the maximum tolerated fraction dose (MTD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC).

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Non-small cell lung cancer confirmed by histology.
* Tumor size is measured according to RECIST standard.
* Unresectable stage IIIA (N2) and IIIB/IIIC, confirmed by PET-CT/or chest and abdomen CT, brain MRI, and whole body bone scan.
* 18-75 years old, regardless of gender.
* The ECOG score is 0-1.
* Newly treated or underwent neoadjuvant chemotherapy and/or immunotherapy.
* Have not received chest radiotherapy in the past.
* Serum hemoglobin ≥10 mg/dL, platelets ≥100000/μL, absolute neutrophil count ≥1500/μL.
* Serum creatinine ≤1.25 times UNL or creatinine clearance ≥60 ml/min.
* Serum bilirubin ≤1.5 times UNL, AST (SGOT) and ALT (SGPT) ≤2.5 times UNL, alkaline phosphatase≤ 5 times UNL.
* FEV1\>1 L.
* CB6 normal range.
* The patient and his family members agree and sign an informed consent form.

Exclusion Criteria:

* Other malignant tumors in the past or during treatment, except for non-melanoma of the skin or carcinoma in situ of the cervix.
* Any other diseases or conditions are contraindications to chemotherapy (such as active infection, within 6 months after myocardial infarction, symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy).
* Pregnant or breastfeeding women, women who have not undergone a pregnancy test (within 14 days before the first dose), and pregnant women.
* Those who are pregnant, breastfeeding or have fertility but have not taken contraceptive measures.
* People with bleeding tendency.
* Those who participated in other clinical trials within 30 days before participating in this experiment.
* Drug addiction, long-term alcoholism, and AIDS patients.
* People with uncontrollable seizures or loss of self-control due to mental illness.
* People with a history of severe allergies or specific physique.
* The researcher believes that the patient is inappropriate to participate in this trial.

Exit criteria

* The treatment cannot be carried out in accordance with the requirements of the research protocol;
* The patient has an allergic reaction ≥ grade 4 or a serious adverse reaction to the study drug;
* The patient is pregnant or has not used adequate contraceptive measures;
* The researcher judges that the patient should not continue to participate the clinical trial;
* The subject asked to withdraw.

• BACKGROUNDAntonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8. PMID 28885881
• BACKGROUNDGray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Ozguroglu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. doi: 10.1016/j.jtho.2019.10.002. Epub 2019 Oct 14. PMID 31622733
• BACKGROUNDCannon DM, Mehta MP, Adkison JB, Khuntia D, Traynor AM, Tome WA, Chappell RJ, Tolakanahalli R, Mohindra P, Bentzen SM, Cannon GM. Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4343-8. doi: 10.1200/JCO.2013.51.5353. Epub 2013 Oct 21. PMID 24145340
• BACKGROUNDUitterhoeve AL, Belderbos JS, Koolen MG, van der Vaart PJ, Rodrigus PT, Benraadt J, Koning CC, Gonzalez Gonzalez D, Bartelink H. Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. European Organization for Research and Treatment of Cancer. Eur J Cancer. 2000 Mar;36(5):592-600. doi: 10.1016/s0959-8049(99)00315-9. PMID 10738123
• BACKGROUNDGraham MV, Pajak TE, Herskovic AM, Emami B, Perez CA. Phase I/II study of treatment of locally advanced (T3/T4) non-oat cell lung cancer with concomitant boost radiotherapy by the Radiation Therapy Oncology Group (RTOG 83-12): long-term results. Int J Radiat Oncol Biol Phys. 1995 Feb 15;31(4):819-25. doi: 10.1016/0360-3016(94)00543-5.