Prevention of Radiation Pneumonitis After Three-Dimensional Conformal Radiation Therapy (3D-CRT) in Patients With Non-Small-Cell Lung Cancer

Condition(s) targeted: Carcinoma, Non-Small-Cell Lung

Intervention: Free breathing (Radiation); Breath holding (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: Centre Leon Berard

Official(s) and/or principal investigator(s):
Line CLAUDE, MD, Principal Investigator, Affiliation: Centre Leon Berard, Lyon

Overall contact:
Sophie DUSSART, MD, Phone: +33 478 78 27 52, Email: dussart@lyon.fnclcc.fr

The purpose of this study is to evaluate the interest of breath holding for the prevention of radiation pneumonitis following conformal radiation therapy.

Eligible patients will be randomly assigned in a 2-arm trial to free breathing or breath holding during conformal radiation.

The primary objective of the study is to establish the efficacy of breath holding, compared to free breathing, in the prevention of early pulmonary toxicity following conformal radiation.

Several departments of radiotherapy, many pneumology units and two basic and applied research laboratories take part in this multicentric study.

The number of patients required to demonstrate a reduction in radiation pneumonitis from 45 % to 22. 5 %, assuming an alpha risk of 5% in a two-sided test and 95% power, is 240 (120 per arm). With a planned accrual of 7 patients per month, it is estimated that the inclusion period should be approximately 3 years.

Official title: Evaluation of the Interest of Breath Holding for the Prevention of Radiation Pneumonitis Following Conformal Radiation Therapy

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Clinical, functional and radiological evaluations at 6-8 weeks and 10-12 weeks after the end of irradiation

Secondary outcome: RTOG and LENT-SOMA scores at 6-8 weeks and 10-12 weeks after the end of irradiation, response rates at 6-8 weeks, 1 year and 2 years after irradiation

Detailed description: The secondary objectives are:

- Validation of the Lent-Soma toxicity scale by comparison to the RTOG scale,

- Response rate at different times: week 6-8, 1 year and 2 years after the end of

irradiation,

- Progression-free survival rate at 1 year and 2 years after the end of irradiation

- Confirmation of the predictive value of serum cytokine levels (IL-6 and IL-10) during

irradiation for the occurrence of early radiation toxicity, and analysis of the correlation between these serum levels at inclusion and the expression polymorphism of candidate genes.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Non-metastatic cytologically or histologically proven non-small-cell lung cancer

(NSCLC)

- Operated NSCLC patients requiring post-surgical irradiation or non-operated NSCLC

patients requiring curative irradiation

- Conformational thoracic radiotherapy with curative intent

- Age >= 18

- Complete functional respiratory evaluation (FRE) performed less than 2 months before

inclusion, demonstrating a maximum expiratory flow-volume/second > 1 l (in case surgery, the FRE must have been realized in the post-surgery period)

- Thoracic CT-scan performed less than 2 months before inclusion for non-operated

patient

- PET-scan performed less than 2 months before inclusion for non-operated patient

- Performance status (PS) ECOG <= 1

- Possible training on breath holding technique

- Female patients of childbearing potential: effective method of contraception

necessary

- Mandatory affiliation with a social security system

- Written, signed, informed consent

Exclusion Criteria:

- Small-cell lung cancer

- Metastatic disease

- Infiltrating pulmonary disease

- Previous thoracic irradiation

- Indication of irradiation with palliative intent

- Previous or concurrent primary malignancies at other sites (except basocellular skin

cancer or cervical cancer in situ or complete remission for more than 5 years)

- Life expectancy < 6 months

- Patient understanding incompatible with the breath-hold technique (patients with major

presbycusis are not eligible)

- Pregnant or lactating woman

- Patient included in another clinical trial

- Follow-up difficult

- Patient deprived of freedom

Sophie DUSSART, MD, Phone: +33 478 78 27 52, Email: dussart@lyon.fnclcc.fr

Centre Léon Bérard, LYON 69008, France; Recruiting
Line CLAUDE, MD, Phone: +33 478 78 26 49, Email: claude@lyon.fnclcc.fr
Séverine GUILLEMAUT, Phone: +33 478 78 29 68, Email: denizot@lyon.fnclcc.fr
Christian CARRIE, MD, Sub-Investigator
Isabelle MARTEL-LAFAY, MD, Sub-Investigator

Institut Curie, PARIS 75005, France; Recruiting
Sylvie HELFRE, MD, Phone: + 33 144 32 46 26, Email: sylvie.helfre@curie.net
Sylvie HELFRE, MD, Principal Investigator

Hôpital Européen Georges Pompidou, PARIS 75015, France; Recruiting
Catherine DURDUX, MD, Phone: +33 156 09 34 05, Email: catherine.durdux@egp.aphp.fr
Catherine DURDUX, MD, Principal Investigator

Hôpital de la Pitié Salpêtrière, PARIS 75013, France; Active, not recruiting

Centre René Gauducheau, SAINT HERBLAIN 44805, France; Recruiting
Marc MAHE, MD, Phone: +33 240 67 99 00, Email: ma-mahe@nantes.fnclcc.fr
Marc MAHE, MD, Principal Investigator
Etienne BARDET, MD, Sub-Investigator
François THILLAYS, MD, Sub-Investigator

Centre Oscar Lambret, LILLE 59020, France; Recruiting
Bernard PREVOST, MD, Phone: +33 320 29 55 53, Email: b-prevost@o-lambret.fr

Related publications:

Arpin D, Perol D, Blay JY, Falchero L, Claude L, Vuillermoz-Blas S, Martel-Lafay I, Ginestet C, Alberti L, Nosov D, Etienne-Mastroianni B, Cottin V, Perol M, Guerin JC, Cordier JF, Carrie C. Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis. J Clin Oncol. 2005 Dec 1;23(34):8748-56.

Claude L, Perol D, Ginestet C, Falchero L, Arpin D, Vincent M, Martel I, Hominal S, Cordier JF, Carrie C. A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis. Radiother Oncol. 2004 May;71(2):175-81.

Starting date: July 2006
Ending date: July 2013
Last updated: February 8, 2008