Bevacizumab After Chemoradiotherapy For Locally Advanced Lung Adenocarcinoma

Lung Adenocarcinoma Clinical Trial

Official title:

A Single-armed Phase Ⅱ Study of Bevacizumab Maintenance Therapy After Chemoradiotherapy for Locally Advanced Lung Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03904563
• Other study ID #: GASTO-1046
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2019
• Est. completion date: December 15, 2022

Study information

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

Clinical Trial Summary

This prospective phase II study is to determine the efficacy and safety of bevacizumab maintenance therapy after concurrent chemoradiotherapy in locally advanced lung adenocarcinoma

Description:

This prospective phase II study is to determine the efficacy and safety of bevacizumab maintenance therapy after concurrent chemoradiotherapy in locally advanced lung adenocarcinoma.

All patients received 4 cycles of weekly docetaxel (25mg/㎡) and nedaplatin (25mg/㎡)(DP), each of 1 day's duration, combined with split-course thoracic radiotherapy, with one-month break.Bevacizumab maintenance therapy starts 1-2 months later after the chemotherapy.The recommended dose for intravenous infusion is 15mg/kg body weight, and the drug is given every 3 weeks for up to 1 year. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 15, 2022
• Est. primary completion date: December 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologic confirmation of lung adenocarcinoma

• Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• Unresectable, refusing surgery or after R2 surgery ,confirmed by PET-CT or chest and abdominal CT, craniocerebral MRI, and ECT.

• After radiotherapy and chemotherapy, the tumor is in partial remission, complete remission or stable.

• 1-2 months after chemoradiotherapy ends.

• Organ and bone marrow functions were normal within the first 30 days of enrollment, including: • AST, ALT= 2.5*ULN or =5*ULN (with liver metastasis); • TBil = 1.5 ULN • neutrophils absolute value =500 cells/mm3 • creatinine clearance =45 mL/min ;• platelets=50,000 cells/mm3.

• CB6 within normal limits

• Patients and their family signed the informed consents

Exclusion Criteria:

• Lung squamous carcinoma.

• The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava).

• The tumor was associated with a cavity over 2cm in diameter.

• Bleeding tendency or coagulation disorder.

• Patients with hemoptysis (1/2 teaspoon blood/day) within 1 month.

• Full-dose anticoagulation therapy was used within the past 1 month.

• Severe vascular disease occurred within 6 months.

• Gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months.

• Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months.

• Uncontrolled hypertension (systolic > 150mmHg and/or diastolic > 100mmHg).

• Major surgery within 28 days or minor surgery or needle biopsy within 48 hours.

• Urine protein 3-4+, or 24h urine protein quantitative >1g.

• Degree 3 esophagitis after chemoradiotherapy has not recovered.

• Elderly patients (age 75 years).

• The investigator does not consider the participant to be eligible for this study.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Lung Adenocarcinoma

Intervention

Drug:
• Bevacizumab
Patients are treated with Bevacizumab 1-2 months after the chemoradiotherapy.The recommended dose for intravenous infusion is 15mg/kg body weight, which is given every 3 weeks for up to 1 year.

Radiation:
• chest radiation
split-course chest radiation

Drug:
• concurrent chemotherapy
weekly docetaxel(25mg/?) and nedaplatin(25mg/?) concurrent with chest radiation

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 (13)

Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non-Small-Cell Lung Cancer: KCSG-LU05-04. J Clin Oncol. 2015 Aug 20;33(24):2660-6. doi: 10.1200/JCO.2014.60.0130. Epub 2015 Jul 6. — 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

Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16. — View Citation

Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, Bogart JA, Dobelbower MC, Bosch W, Galvin JM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Raben A, Augspurger ME, MacRae RM, Paulus R, Bradley JD. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol. 2017 Jan;35(1):56-62. doi: 10.1200/JCO.2016.69.1378. Epub 2016 Oct 31. — View Citation

Gallet P, Phulpin B, Merlin JL, Leroux A, Bravetti P, Mecellem H, Tran N, Dolivet G. Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring. PLoS One. 2011;6(12):e29399. doi: 10.1371/journal.pone.0029399. Epub 2011 Dec 22. — View Citation

Nadler E, Yu E, Ravelo A, Sing A, Forsyth M, Gruschkus S. Bevacizumab treatment to progression after chemotherapy: outcomes from a U.S. community practice network. Oncologist. 2011;16(4):486-96. doi: 10.1634/theoncologist.2010-0287. Epub 2011 Mar 25. — View Citation

Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009 Mar 10;27(8):1227-34. doi: 10.1200/JCO.2007.14.5466. Epub 2009 Feb 2. Erratum In: J Clin Oncol. 2009 May 10;27(14):2415. — View Citation

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884. Erratum In: N Engl J Med. 2007 Jan 18;356(3):318. — View Citation

Spigel DR, Hainsworth JD, Yardley DA, Raefsky E, Patton J, Peacock N, Farley C, Burris HA 3rd, Greco FA. Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol. 2010 Jan 1;28(1):43-8. doi: 10.1200/JCO.2009.24.7353. Epub 2009 Nov 9. — View Citation

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4. — View Citation

Tsujino K, Kurata T, Yamamoto S, Kawaguchi T, Kubo A, Isa S, Hasegawa Y, Ou SH, Takada M, Ando M. Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature. J Thorac Oncol. 2013 Sep;8(9):1181-9. doi: 10.1097/JTO.0b013e3182988348. — View Citation

Wozniak AJ, Moon J, Thomas CR Jr, Kelly K, Mack PC, Gaspar LE, Raben D, Fitzgerald TJ, Pandya KJ, Gandara DR. A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Combination of Bevacizumab (NSC-704865) in Patients With Inoperable Locally Advanced Stage III Non-Small-Cell Lung Cancer: SWOG S0533. Clin Lung Cancer. 2015 Sep;16(5):340-7. doi: 10.1016/j.cllc.2014.12.014. Epub 2015 Jan 9. — View Citation

Zhou C, Wu YL, Chen G, Liu X, Zhu Y, Lu S, Feng J, He J, Han B, Wang J, Jiang G, Hu C, Zhang H, Cheng G, Song X, Lu Y, Pan H, Zheng W, Yin AY. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Jul 1;33(19):2197-204. doi: 10.1200/JCO.2014.59.4424. Epub 2015 May 26. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Progression-free survival in patients	3-year
Primary	rate of grade=2 radiation pneumonia(NCI-CTC4.0)	radiation-induced pulmonary injury is classified into 1-5 grades according to NCI-CTC4.0. The incidence of symptomatic radiation-induced pulmonary injury: the ratio of grade 2 and above radiation-induced pulmonary injury cases in 1 year after radio therapy to all cases can be evaluated .	1 year from the end of chemoradiotherapy
Secondary	overall survival	overall survival	3-year
Secondary	response rate		3-year
Secondary	rate of grade 3-4 radiation esophagitis		3-year
Secondary	rate of grade 3-4 radiation pneumonitis		3-year