IMRT Combined With Erlotinib for EGFR Wild Type Non-small Cell Lung Cancer With 4-10 Brain Metastases

Non-Small Cell Lung Carcinoma Clinical Trial

Official title:

IMRT Combined With Erlotinib Compared With Whole-brain Radiotherapy for EGFR Wild Type Non-small Cell Lung Cancer With 4-10 Brain Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02556593
• Other study ID #: GASTO1009
• Status: Terminated
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: April 2019

Study information

• Verified date: April 2019
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to assess the efficacy of IMRT combined with erlotinib compared with whole-brain radiotherapy for EGFR wild type non-small cell lung cancer with 4-10 brain metastases.

Description:

This study is to assess the efficacy of IMRT combined with erlotinib compared with whole-brain radiotherapy for EGFR wild type non-small cell lung cancer with 4-10 brain metastases.

All patients recruited will be randomly assigned into two groups. Patients in experimental group will receive daily IMRT at 45 Gy in 15 fractions to brain metastases, combined with daily erlotinib of 150mg for three weeks. Patients in control group will receive daily whole-brain radiotherapy at 30 Gy in 10 fractions.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed NSCLC and wild type EGFR

• 4-10 brain metastases on high quality CT scanning or MRI.

• No previous EGFR-TKI treatment.

• No previous brain radiotherapy.

• More than 4 weeks from last chemotherapy.

• Expected Survival of at least 2 months.

• KPS= 70

• RTOG RPA performance status 0-1

• Lab tests should meet these criteria: White blood cell count =3×10^9 /L;Platelet count=100×10^9 /L;Total bilirubin 1.5 times or less the upper limits of normal (ULN); AST and ALT 1.5 times or less the ULN; Serum creatinine 1.5 times or less the ULN or creatinine clearance rate(CCR) greater than or equal to 60 ml/min.

• Pregnancy test (-)

• Be able to sign informed consent form.

Exclusion Criteria:

• With unstable systematical diseases (concluding acute infection, grade 4 hypertension, unstable angina pectoris, congestive heart failure, hepatopathy, nephropathy, metabolic diseases)

• With metastases on meninges.

• Taking antiepileptics (phenytoin sodium etc.) at the same time

• Unable to oral medication.

• Previous or recent another malignancy, except for nonmelanoma skin cancer or cervical cancer in situ

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Carcinoma

Intervention

Radiation:
• IMRT
Daily IMRT at 45 Gy in 15 fractions to brain metastases
• WBRT
3DCRT at 30 Gy in 10 fractions to whole brain

Drug:
• erlotinib
erlotinib 150mg daily

Locations

Country	Name	City	State
China	Hui Liu	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (35)

Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. — View Citation

Barsukov VS. [Quantitative description of the process of radiation inactivation of cells. VIII. Microdosimetry in the analysis of the reproductive death of eukaryotic cells]. Tsitologiia. 1977 Sep;19(9):991-9. Russian. — View Citation

Bauman G, Yartsev S, Fisher B, Kron T, Laperriere N, Heydarian M, VanDyk J. Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases. Am J Clin Oncol. 2007 Feb;30(1):38-44. — View Citation

Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):898-903. Epub 2005 Dec 9. — View Citation

Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):996-1001. doi: 10.1016/j.ijrobp.2009.06.006. Epub 2009 Sep 23. — View Citation

Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, Chinnaiyan AM, Harari PM. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res. 2005 Apr 15;65(8):3328-35. — View Citation

Davey P, Hoegler D, Ennis M, Smith J. A phase III study of accelerated versus conventional hypofractionated whole brain irradiation in patients of good performance status with brain metastases not suitable for surgical excision. Radiother Oncol. 2008 Aug;88(2):173-6. doi: 10.1016/j.radonc.2008.05.020. Epub 2008 Jun 12. — View Citation

Edwards AA, Keggin E, Plowman PN. The developing role for intensity-modulated radiation therapy (IMRT) in the non-surgical treatment of brain metastases. Br J Radiol. 2010 Feb;83(986):133-6. doi: 10.1259/bjr/28596848. Epub 2009 Dec 17. — View Citation

El Gantery MM, Abd El Baky HM, El Hossieny HA, Mahmoud M, Youssef O. Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both. Radiat Oncol. 2014 May 20;9:116. doi: 10.1186/1748-717X-9-116. — View Citation

Frazier JL, Batra S, Kapor S, Vellimana A, Gandhi R, Carson KA, Shokek O, Lim M, Kleinberg L, Rigamonti D. Stereotactic radiosurgery in the management of brain metastases: an institutional retrospective analysis of survival. Int J Radiat Oncol Biol Phys. 2010 Apr;76(5):1486-92. doi: 10.1016/j.ijrobp.2009.03.028. Epub 2009 Jul 18. — View Citation

Haie-Meder C, Pellae-Cosset B, Laplanche A, Lagrange JL, Tuchais C, Nogues C, Arriagada R. Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases. Radiother Oncol. 1993 Feb;26(2):111-6. — View Citation

Hendriks LE, Troost EG, Steward A, Bootsma GP, De Jaeger K, van den Borne BE, Dingemans AM. Patient selection for whole brain radiotherapy (WBRT) in a large lung cancer cohort: Impact of a new Dutch guideline on brain metastases. Acta Oncol. 2014 Jul;53(7):945-51. doi: 10.3109/0284186X.2014.906746. Epub 2014 Apr 23. — View Citation

Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011 Jan 10;29(2):134-41. doi: 10.1200/JCO.2010.30.1655. Epub 2010 Nov 1. — View Citation

Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):427-34. — View Citation

Lagerwaard FJ, van der Hoorn EA, Verbakel WF, Haasbeek CJ, Slotman BJ, Senan S. Whole-brain radiotherapy with simultaneous integrated boost to multiple brain metastases using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):253-9. doi: 10.1016/j.ijrobp.2009.03.029. Epub 2009 Jul 4. — View Citation

Meany HJ, Fox E, McCully C, Tucker C, Balis FM. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates. Cancer Chemother Pharmacol. 2008 Aug;62(3):387-92. Epub 2007 Oct 12. — View Citation

Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, Romano A, Enrici RM. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011 May 15;6:48. doi: 10.1186/1748-717X-6-48. — View Citation

Park SH, Hwang SK, Kang DH, Lee SH, Park J, Hwang JH, Hamm IS, Park YM. Gamma knife radiosurgery for multiple brain metastases from lung cancer. J Clin Neurosci. 2009 May;16(5):626-9. doi: 10.1016/j.jocn.2008.08.003. Epub 2009 Mar 5. — View Citation

Park SJ, Kim HT, Lee DH, Kim KP, Kim SW, Suh C, Lee JS. Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation. Lung Cancer. 2012 Sep;77(3):556-60. doi: 10.1016/j.lungcan.2012.05.092. Epub 2012 Jun 5. — View Citation

Pesce GA, Klingbiel D, Ribi K, Zouhair A, von Moos R, Schlaeppi M, Caspar CB, Fischer N, Anchisi S, Peters S, Cathomas R, Bernhard J, Kotrubczik NM, D'Addario G, Pilop C, Weber DC, Bodis S, Pless M, Mayer M, Stupp R. Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). Eur J Cancer. 2012 Feb;48(3):377-84. doi: 10.1016/j.ejca.2011.10.016. Epub 2011 Nov 15. — View Citation

Porta R, Sánchez-Torres JM, Paz-Ares L, Massutí B, Reguart N, Mayo C, Lianes P, Queralt C, Guillem V, Salinas P, Catot S, Isla D, Pradas A, Gúrpide A, de Castro J, Polo E, Puig T, Tarón M, Colomer R, Rosell R. Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J. 2011 Mar;37(3):624-31. doi: 10.1183/09031936.00195609. Epub 2010 Jul 1. — View Citation

Rades D, Kieckebusch S, Lohynska R, Veninga T, Stalpers LJ, Dunst J, Schild SE. Reduction of overall treatment time in patients irradiated for more than three brain metastases. Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1509-13. Epub 2007 Aug 6. — View Citation

Raldow AC, Chiang VL, Knisely JP, Yu JB. Survival and intracranial control of patients with 5 or more brain metastases treated with gamma knife stereotactic radiosurgery. Am J Clin Oncol. 2013 Oct;36(5):486-90. doi: 10.1097/COC.0b013e31825494ef. — View Citation

Serizawa T, Iuchi T, Ono J, Saeki N, Osato K, Odaki M, Ushikubo O, Hirai S, Sato M, Matsuda S. Gamma knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy. J Neurosurg. 2000 Dec;93 Suppl 3:32-6. — View Citation

Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):291-8. — View Citation

Tanaka T, Munshi A, Brooks C, Liu J, Hobbs ML, Meyn RE. Gefitinib radiosensitizes non-small cell lung cancer cells by suppressing cellular DNA repair capacity. Clin Cancer Res. 2008 Feb 15;14(4):1266-73. doi: 10.1158/1078-0432.CCR-07-1606. — View Citation

Togashi Y, Masago K, Fukudo M, Tsuchido Y, Okuda C, Kim YH, Ikemi Y, Sakamori Y, Mio T, Katsura T, Mishima M. Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol. 2011 Oct;68(4):1089-92. doi: 10.1007/s00280-011-1691-z. Epub 2011 Jun 17. — View Citation

Togashi Y, Masago K, Masuda S, Mizuno T, Fukudo M, Ikemi Y, Sakamori Y, Nagai H, Kim YH, Katsura T, Mishima M. Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer. Cancer Chemother Pharmacol. 2012 Sep;70(3):399-405. doi: 10.1007/s00280-012-1929-4. Epub 2012 Jul 18. — View Citation

Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012 Apr 18;(4):CD003869. doi: 10.1002/14651858.CD003869.pub3. Review. Update in: Cochrane Database Syst Rev. 2018 Jan 25;1:CD003869. — View Citation

Wang M, Jing Z, Mingjiang C. Cerebral penetration of gefitinib in patients with lung adenocarcinoma[J]. J Clin Oncol, 2011, 29(suppl); abstr7608

Wang M, Morsbach F, Sander D, Gheorghiu L, Nanda A, Benes C, Kriegs M, Krause M, Dikomey E, Baumann M, Dahm-Daphi J, Settleman J, Willers H. EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks. Cancer Res. 2011 Oct 1;71(19):6261-9. doi: 10.1158/0008-5472.CAN-11-0213. Epub 2011 Aug 18. — View Citation

Welsh JW, Komaki R, Amini A, Munsell MF, Unger W, Allen PK, Chang JY, Wefel JS, McGovern SL, Garland LL, Chen SS, Holt J, Liao Z, Brown P, Sulman E, Heymach JV, Kim ES, Stea B. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol. 2013 Mar 1;31(7):895-902. doi: 10.1200/JCO.2011.40.1174. Epub 2013 Jan 22. — View Citation

Wu YL, Zhou C, Cheng Y, Lu S, Chen GY, Huang C, Huang YS, Yan HH, Ren S, Liu Y, Yang JJ. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol. 2013 Apr;24(4):993-9. doi: 10.1093/annonc/mds529. Epub 2012 Nov 4. — View Citation

Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10. — View Citation

Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Devel Ther. 2013 Oct 8;7:1179-86. doi: 10.2147/DDDT.S53011. eCollection 2013. — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CNS progression free survival		2 years