Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

Locally Advanced Lung Carcinoma Clinical Trial

Official title:

Fraction Dose Escalation of Hypofractionated Radiotherapy With Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-small Cell Lung Cancer: a Phase 1 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04951063
• Other study ID #: GASTO-1080
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: December 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: September 30, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Lung Carcinoma
• Lung Neoplasms

Intervention

Radiation:
• Hypofractionated radiotherapy
Split-course adaptive HRT-CHT is administered at the following three dose levels: Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course,DT 1500cGy/5 daily fractions/300cGy in the second course; Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course, DT 2000cGy/5 daily fractions/400cGy in the second course; Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course, DT 3000cGy/6 daily fractions/500cGy in the second course.

Drug:
• Concurrent chemotherapy
weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT
• Consolidation immunotherapy
Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (15)

Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009 Aug 1;374(9687):379-86. doi: 10.1016/S0140-6736(09)60737-6. Epub 2009 Jul 24. — View Citation

Antonia 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. — View Citation

Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. doi: 10.1200/JCO.2005.55.405. Epub 2005 Aug 8. Erratum In: J Clin Oncol. 2006 Apr 20;24(12):1966. — View Citation

Cannon 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. — View Citation

Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. doi: 10.1200/JCO.1999.17.9.2692. — View Citation

Gielda BT, Marsh JC, Zusag TW, Faber LP, Liptay M, Basu S, Warren WH, Fidler MJ, Batus M, Abrams RA, Bonomi P. Split-course chemoradiotherapy for locally advanced non-small cell lung cancer: a single-institution experience of 144 patients. J Thorac Oncol. 2011 Jun;6(6):1079-86. doi: 10.1097/JTO.0b013e3182199a7c. — View Citation

Glinski K, Socha J, Wasilewska-Tesluk E, Komosinska K, Kepka L. Accelerated hypofractionated radiotherapy with concurrent full dose chemotherapy for locally advanced non-small cell lung cancer: A phase I/II study. Radiother Oncol. 2020 Jul;148:174-180. doi: 10.1016/j.radonc.2020.04.033. Epub 2020 Apr 24. — View Citation

Graham 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. — View Citation

Gray 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. — View Citation

Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008 Dec 10;26(35):5755-60. doi: 10.1200/JCO.2008.17.7840. Epub 2008 Nov 10. — View Citation

Kong C, Zhu X, Shi M, Wang L, Chen C, Tao H, Jiang N, Yan P, Zhao L, Song X, He X. Survival and Toxicity of Hypofractionated Intensity Modulated Radiation Therapy in 4 Gy Fractions for Unresectable Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):710-719. doi: 10.1016/j.ijrobp.2020.03.038. Epub 2020 Apr 7. — View Citation

Qiu B, Li QW, Ai XL, Wang B, Huan J, Zhu ZF, Yu GH, Ji M, Jiang HH, Li C, Zhang J, Chen L, Guo JY, Zhou Y, Liu H. Investigating the loco-regional control of simultaneous integrated boost intensity-modulated radiotherapy with different radiation fraction sizes for locally advanced non-small-cell lung cancer: clinical outcomes and the application of an extended LQ/TCP model. Radiat Oncol. 2020 May 27;15(1):124. doi: 10.1186/s13014-020-01555-x. — View Citation

Spoelstra FO, Pantarotto JR, van Sornsen de Koste JR, Slotman BJ, Senan S. Role of adaptive radiotherapy during concomitant chemoradiotherapy for lung cancer: analysis of data from a prospective clinical trial. Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1092-7. doi: 10.1016/j.ijrobp.2008.12.027. Epub 2009 Mar 26. — View Citation

Uitterhoeve 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. — View Citation

Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; Cancer and Leukemia Group B. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. doi: 10.1200/JCO.2006.07.3569. Epub 2007 Apr 2. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the maximally tolerated fraction dose	The maximum tolerated fraction dose was defined as the highest DL in which <=2 patients of the 6 treated patients experienced G3+ toxicity and <=1 patient experienced G4+ toxicity within 12 months after RT. If a patient had multiple types of toxicities, only the highest grade of toxicity was counted.	1 year
Secondary	Objective response rate	Proportion of patients with PR and CR at 2 months after radiotherapy	2 months after radiotherapy
Secondary	Overall survival		1-year
Secondary	Progression-free survival		1-year
Secondary	Distant-metastasis free survival		1-year
Secondary	Loco-regional recurrence-free survival		1-year