search
Back to results

Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

Primary Purpose

Locally Advanced Lung Carcinoma

Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Hypofractionated radiotherapy
Concurrent chemoradiotherapy
Consolidation immunotherapy
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Lung Carcinoma focused on measuring Locally advanced non-small cell lung cancer, Definitive hypofractionated chemoradiotherapy, Fraction dose escalation, Consolidation immunotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sun yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Split-course adaptive HRT-CHT

Arm Description

In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 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. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.

Outcomes

Primary Outcome Measures

Treatment-induced ≥ Grade 3 toxicity (CTCAE 5.0 version)
Grade 3 hematological toxicity, any level allergic reactions of drugs, and grade 3 radiation esophagitis are not considered dose-limiting toxicity

Secondary Outcome Measures

Objective response rate
Proportion of patients with PR and CR at 2 months after radiotherapy
Progression-free survival

Full Information

First Posted
June 26, 2021
Last Updated
November 25, 2022
Sponsor
Sun Yat-sen University
search

1. Study Identification

Unique Protocol Identification Number
NCT04951063
Brief Title
Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC
Official Title
Fraction Dose Escalation of Split-course Adaptive Hypo-fractionated Concurrent Chemoradiotherapy in Locally Advanced NSCLC: a Phase I Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
January 31, 2023 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
We aim to improve local control by escalating the fraction dose of accelerated hypofractionated radiotherapy (HRT) with concurrent chemotherapy (CHT). In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Lung Carcinoma
Keywords
Locally advanced non-small cell lung cancer, Definitive hypofractionated chemoradiotherapy, Fraction dose escalation, Consolidation immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Split-course adaptive HRT-CHT
Arm Type
Experimental
Arm Description
In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 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. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated radiotherapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Concurrent chemoradiotherapy
Intervention Description
weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT
Intervention Type
Drug
Intervention Name(s)
Consolidation immunotherapy
Intervention Description
Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
Primary Outcome Measure Information:
Title
Treatment-induced ≥ Grade 3 toxicity (CTCAE 5.0 version)
Description
Grade 3 hematological toxicity, any level allergic reactions of drugs, and grade 3 radiation esophagitis are not considered dose-limiting toxicity
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Proportion of patients with PR and CR at 2 months after radiotherapy
Time Frame
2 months after radiotherapy
Title
Progression-free survival
Time Frame
2-year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hui Liu, Professor
Organizational Affiliation
Sun yat-sen universtiy cancer center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
28885881
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.
Results Reference
background
PubMed Identifier
31622733
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.
Results Reference
background
PubMed Identifier
24145340
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.
Results Reference
background
PubMed Identifier
10738123
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.
Results Reference
background
PubMed Identifier
7860394
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.
Results Reference
background
PubMed Identifier
32460796
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.
Results Reference
background
PubMed Identifier
32388152
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.
Results Reference
background
PubMed Identifier
32275994
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.
Results Reference
background
PubMed Identifier
19001323
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.
Results Reference
background
PubMed Identifier
19327915
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.
Results Reference
background
PubMed Identifier
21532501
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.
Results Reference
background
PubMed Identifier
10561343
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.
Results Reference
background
PubMed Identifier
16087941
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.
Results Reference
background
PubMed Identifier
19632716
Citation
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.
Results Reference
background
PubMed Identifier
17404369
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.
Results Reference
background

Learn more about this trial

Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

We'll reach out to this number within 24 hrs