Proton Therapy With Chemotherapy for Stage III Non-Small Cell Lung Cancer (LU02)

Non-Small Cell Lung Cancer Clinical Trial

— LU02  

Official title:

A Phase II Trial of 3 Dimensional Proton Radiotherapy With Concomitant Chemotherapy for Patients With Initially Unresectable Stage III Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00881712
• Other study ID #: UFPTI 0802-LU02
• Status: Terminated
• Phase: Phase 2
• First received: April 13, 2009
• Last updated: February 8, 2016
• Start date: June 2009
• Est. completion date: October 2014

Study information

• Verified date: February 2016
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out what effects, good and/or bad, proton radiation at a higher tumor dose (and lower normal surrounding lung dose) combined with standard chemotherapy has on lung cancer. The dose you receive to the tumor will be higher than the standard dose. This may be able to increase the control of the tumor. Due to the accuracy of radiation given with protons, the dose to the normal lung tissue that surrounds the tumor will be lower than standard. This may be able to reduce the frequency and severity of the usual radiation side effects.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented non-small cell carcinoma of the lung diagnosed within 16 weeks prior to study enrollment.

• Patient must be at least 18 years old at the time of consent.

• Stage III A or III B disease.

• Patients must be able to start study treatment within 6 weeks of study enrollment.

• Induction chemotherapy is allowed.

• Marginally resectable or unresectable at presentation.

• If the patient had exploratory thoracotomy, it must be done at least 3 weeks prior to enrollment.

Exclusion Criteria:

• Evidence of distant metastasis.

• Prior thoracic radiotherapy.

• Any history of allergic reaction to taxanes.

• Prior tumor resection. Candidate for upfront curative surgery.

• Pleural effusion visible on chest x-ray or the scout view of the CT chest.

• Unintentional weight loss within the month prior to diagnosis = 10%.

• Previous or concomitant malignancy other than early stage tumor treated more than 3 years ago for cure.

• The presence of PET positive contralateral hilar disease.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Radiation:
• PET positive nodal disease measuring 15 mm or greater
Proton radiation at 2 cobalt gray equivalent per fraction to a total of 74 cobalt gray equivalent with concomitant weekly chemotherapy.
• PET positive nodal disease measuring less than 15 mm
Proton radiation at 2 cobalt gray equivalent per fraction to a total of 60 cobalt gray equivalent with concomitant weekly chemotherapy.
• Patients considered resectable
Proton radiation at 2 cobalt gray per fraction. Re-evaluation performed between days 18-22 of treatment. If considered resectable after re-evaluation, radiotherapy will discontinue after a total of 50 cobalt gray equivalent and surgery will be performed.

Locations

Country	Name	City	State
United States	University of Florida Proton Therapy Institute	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (25)

Albain KS, Swann RS, Rusch VR, et al. Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs. CT/RT followed by surgical resection for stage IIIA (pN2) non-small cell lung cancer (NSCLC): Outcomes update of North American Intergroup 0139 (RTOG 9309). Proc Am Soc Clin Oncol, abstract 7014, 2005.

Auberger T, Seydl K, Futschek T, Sztankay A, Sweeney RA, Lukas P. Photons or protons: precision radiotherapy of lung cancer. Strahlenther Onkol. 2007 Dec;183 Spec No 2:3-6. doi: 10.1007/s00066-007-2002-9. — 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. Epub 2005 Aug 8. Erratum in: J Clin Oncol. 2006 Apr 20;24(12):1966. — View Citation

Blackstock A. Cancer and Leukemia Group B: Induction plus concurrent chemotherapy with high dose (74 Gy) 3 dimensional (3-D) thoracic radiotherapy in stage III non-small cell lung cancer. Preliminary report of CALGB 30105. Pro Amer Soc Clin Oncol. 24(1): 7042, 2006.

Bradley J, et al. Phase I results of RTOG 0117; A phase I/II dose intensification study using 3DCRTand concurrent chemotherapy for patients with inoperable non-small cell lung cancer. Pro Amer Soc Clin Oncol. 24: p. 7063A, 2005.

Chang JY, Zhang X, Wang X, Kang Y, Riley B, Bilton S, Mohan R, Komaki R, Cox JD. Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1087-96. Epub 2006 May 6. — View Citation

Chapet O, Kong FM, Quint LE, Chang AC, Ten Haken RK, Eisbruch A, Hayman JA. CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):170-8. — View Citation

Choy H, Akerley W, Safran H, Graziano S, Chung C, Williams T, Cole B, Kennedy T. Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. J Clin Oncol. 1998 Oct;16(10):3316-22. — View Citation

Chvetsov AV, Palta JJ, Nagata Y. Time-dependent cell disintegration kinetics in lung tumors after irradiation. Phys Med Biol. 2008 May 7;53(9):2413-23. doi: 10.1088/0031-9155/53/9/013. Epub 2008 Apr 17. — View Citation

Curran W, Scott C, Langer C, et al. Long term benefit is observed in a phase III comparison of sequential vs. concurrent chemo-radiation for patients with unresectable NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 2003;61(abstr).

Delaney, Kooy editors: Proton and Charged particle Radiotherapy; LWW, 2008

Fletcher GH. Clinical dose-response curves of human malignant epithelial tumours. Br J Radiol. 1973 Jan;46(541):1-12. — 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. — View Citation

Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, Perez CA. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):323-9. — View Citation

Komaki R, Sejpal S, Wei X, et al. Reduction of Bone Marrow Suppression for Patients with Stage III NSCLC Treated by Proton and Chemotherapy Compared with IMRT and Chemotherapy. Proceedings of the PTCOG 47, May 19-24, 2008.

Lau D, Leigh B, Gandara D, Edelman M, Morgan R, Israel V, Lara P, Wilder R, Ryu J, Doroshow J. Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial. J Clin Oncol. 2001 Jan 15;19(2):442-7. — View Citation

Lee HK, Vaporciyan AA, Cox JD, Tucker SL, Putnam JB Jr, Ajani JA, Liao Z, Swisher SG, Roth JA, Smythe WR, Walsh GL, Mohan R, Liu HH, Mooring D, Komaki R. Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters. Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1317-22. — View Citation

Martel MK, et al. Incidental doses to clinically negative nodes from conformal treatment fields for non-small cell lung cancer. Int J Rad Oncol Biol Phys. 45(3 (supplement)): 244, 1999.

Nichols RC, Henderson RH, Huh SN, Flampouri S, Cury JD, Pham DC, D'Agostino HJ, Louis D, Li Z, Mendenhall NP. Proton Radiotherapy Offers Reduced Bone Marrow and Normal Lung Exposure for Patients Receiving Dose Escalated Radiotherapy with Concomitant Chemotherapy for Regionally Advanced Non-Small Cell Lung Cancer. Presented at the LALCa 2008 - 3rd Latin American Conference on Lung Cancer - Tercera Conferencia Latinoamericana sobre Cancer Pulmonar - Vina del Mar, Chile - October 9 and 10, 2008

Nichols RC, Huh SH, Hoppe BS, Henderson RH, Li Z, Flampouri S, D'Agostino HJ, Cury JD, Pham DC, Mendenhall NP. Protons safely allow coverage of high-risk nodes for patients with regionally advanced non-small-cell lung cancer. Technol Cancer Res Treat. 2011 Aug;10(4):317-22. — View Citation

Perez CA, Pajak TF, Rubin P, Simpson JR, Mohiuddin M, Brady LW, Perez-Tamayo R, Rotman M. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group. Cancer. 1987 Jun 1;59(11):1874-81. — View Citation

Rosenman JG, Halle JS, Socinski MA, Deschesne K, Moore DT, Johnson H, Fraser R, Morris DE. High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):348-56. — View Citation

Rosenzweig KE, Sim SE, Mychalczak B, Braban LE, Schindelheim R, Leibel SA. Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):681-5. — View Citation

Roth JA, Atkinson EN, Fossella F, Komaki R, Bernadette Ryan M, Putnam JB Jr, Lee JS, Dhingra H, De Caro L, Chasen M, Hong WK. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Lung Cancer. 1998 Jul;21(1):1-6. — View Citation

Vokes E, Herndon J, Turrisi A. Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial. Pro Amer Soc Clin Oncol. 23(616A), 2004.

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade 3 or Higher Rate of Non-hematologic, Acute Treatment-related Toxicities		Six months after end of radiation therapy	Yes
Secondary	Percentage of Patients With Disease Control	Disease control rate is defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). As per RECIST version 1.1, Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study."), as accurate.	Following treatment every 6 months for 2 years, then annually for 4 years.	No
Secondary	Percentage of Patients Alive at 5 Years		Five years following radiation treatment	No
Secondary	Feasibility, Safety and Efficacy of Delivering Proton Radiotherapy With Concomitant Chemotherapy		Weekly during treatment, then every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, then annually	Yes
Secondary	Correlation of Functional CT-PET Imaging With Treatment Outcomes		Prestudy, before surgery (if applicable) between days 18-22 if needed, then during follow-up every 6 months for 2 years, then annually for 4 years	No

External Links

•   Contact the University of Florida Proton Therapy Institute