CO(Mbined Therapy of Malignant) S(Alivary Gland tu)M(Ours With)I(MRT and) c(Arbon Ions): COSMIC - Full Text View

Purpose

The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity and efficacy in the combined treatment with intensity-modulated radiation therapy (IMRT) and carbon ion (C12) boost. Primary endpoint is mucositis ≥ CTC°3, secondary endpoints are local control, disease-free survival, and toxicity. Planned accrual of the trial includes 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Treatment consists of 24 GyE carbon ions (8 fractions) and 50 Gy IMRT (2.0 Gy/ fraction).

Condition	Intervention	Phase
Malignancy Salivary Glands Tumor	Radiation: carbon ion boost	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Combined Therapy of Malignant Salivary Gland Tumours With IMRT and Carbon Ions: COSMIC

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by University of Heidelberg:

Primary Outcome Measures:

mucositis ≥ CTC°3 [ Time Frame: 6-8 weeks post completion of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

local control [ Time Frame: 3 years post RT ] [ Designated as safety issue: No ]
to evaluate local control at 3 years post RT
acute toxicity [ Time Frame: 6-8 weeks post completion of treatment ] [ Designated as safety issue: Yes ]
evaluation of acute radiation effects (other than mucositis CTC°C) 6-8 weeks post completion of treatment
late toxicity [ Time Frame: 3 years post radiotherapy ] [ Designated as safety issue: Yes ]
to evaluate radiation late effects
disease-free survival [ Time Frame: 3 years post treatment ] [ Designated as safety issue: No ]
to evaluate disease-free survival at 3 years post radiotherapy

Estimated Enrollment:	54
Study Start Date:	June 2010
Estimated Study Completion Date:	September 2013
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IMRT + C12-boost (8 x 3 GyE) carbon ion therapy followed by 50 Gy IMRT (2 Gy/ Fx)corresponding to a total dose of approximately 74 GyE.	Radiation: carbon ion boost 8 fractions carbon ion (8 x 3 GyE C12) therapy followed by 25 fractions of IMRT corresponding to a total dose of approximately 74 GyE. Treatment duration is approximately 61/2-7 weeks

Detailed Description:

Local control in malignant salivary gland tumours is dose dependent. High local control rates in adenoid cystic carcinomas could be achieved by highly conformal radiotherapy techniques and particle (neutron/ carbon ion) therapy. Considering high doses are needed to achieve local control, all malignant salivary gland tumours probably profit from the use of particle therapy, which in case of carbon ion treatment, has been shown to be accompanied by only mild side-effects.

Methods/ design:

The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity in the combined treatment with intensity-modulated radiation therapy (IMRT) and carbon ion (C12) boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (2.0 Gy/ fraction).

Study objectives:

Incidence of mucositis ≥ CTC°3 will be assessed as the primary endpoint of the trial, local control, disease-free survival, toxicity (incl. mucositis CTC °I-II and late toxicity at 3 years post RT)

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed or surgically removed malignant tumour of the salivary glands (head and neck)
Inoperable tumour
G2/3
Macroscopic or microscopic residual tumour (R2/ R1) or
≥T3/T4 or
perineural invasion (Pn+)
written informed consent
pts aged 18 - 80 years
effective contraception for pts in childbearing age (<12 months post beginning of menopause)

Exclusion Criteria:

Prior radio- or chemotherapy for tumours of the head and neck
Other previous malignancy within the past 5 years except prior, adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
Significant neurological or psychiatric condition including dementia or seizures or other serious medical condition prohibiting the patient's participation in the trial by judgement of the investigators
Legal incapacity or limited legal capacity
Positive serum/ urine beta-HCG/ pregnancy
Drug abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154270

Locations

Germany
Dept. of Radiation Oncology, INF 400
Heidelberg, Germany, 69120

Sponsors and Collaborators

University of Heidelberg

Investigators

Principal Investigator:

Marc W Muenter, MD

Dept. of Radiation Oncology, INF 400, 69120 Heidelberg

More Information

Publications:

Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986 Jan-Feb;8(3):177-84.

Chen AM, Granchi PJ, Garcia J, Bucci MK, Fu KK, Eisele DW. Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):982-7. Epub 2007 Jan 22.

Gurney TA, Eisele DW, Weinberg V, Shin E, Lee N. Adenoid cystic carcinoma of the major salivary glands treated with surgery and radiation. Laryngoscope. 2005 Jul;115(7):1278-82.

Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Hinerman RW, Villaret DB. Radiotherapy alone or combined with surgery for adenoid cystic carcinoma of the head and neck. Head Neck. 2004 Feb;26(2):154-62.

Chen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR, Phillips TL, Fu KK, Eisele DW. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):152-9.

Garden AS, Weber RS, Ang KK, Morrison WH, Matre J, Peters LJ. Postoperative radiation therapy for malignant tumors of minor salivary glands. Outcome and patterns of failure. Cancer. 1994 May 15;73(10):2563-9.

Terhaard CH, Lubsen H, Van der Tweel I, Hilgers FJ, Eijkenboom WM, Marres HA, Tjho-Heslinga RE, de Jong JM, Roodenburg JL; Dutch Head and Neck Oncology Cooperative Group. Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck. 2004 Aug;26(8):681-92; discussion 692-3.

Terhaard CH, Lubsen H, Rasch CR, Levendag PC, Kaanders HH, Tjho-Heslinga RE, van Den Ende PL, Burlage F; Dutch Head and Neck Oncology Cooperative Group. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):103-11.

Bittner N, Koh WJ, Laramore GE, Patel S, Mulligan MS, Douglas JG. Treatment of locally advanced adenoid cystic carcinoma of the trachea with neutron radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):410-4. Epub 2008 Apr 18.

Schulz-Ertner D, Nikoghosyan A, Didinger B, Münter M, Jäkel O, Karger CP, Debus J. Therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques. Cancer. 2005 Jul 15;104(2):338-44.

Douglas JG, Koh WJ, Austin-Seymour M, Laramore GE. Treatment of salivary gland neoplasms with fast neutron radiotherapy. Arch Otolaryngol Head Neck Surg. 2003 Sep;129(9):944-8.

Mizoe JE, Tsujii H, Kamada T, Matsuoka Y, Tsuji H, Osaka Y, Hasegawa A, Yamamoto N, Ebihara S, Konno A; Organizing Committee for the Working Group for Head-And-Neck Cancer. Dose escalation study of carbon ion radiotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):358-64.

Huber PE, Debus J, Latz D, Zierhut D, Bischof M, Wannenmacher M, Engenhart-Cabillic R. Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam? Radiother Oncol. 2001 May;59(2):161-7.

Münter MW, Schulz-Ertner D, Hof H, Nikoghosyan A, Jensen A, Nill S, Huber P, Debus J. Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment. Radiat Oncol. 2006 Jun 6;1:17.

Pommier P, Liebsch NJ, Deschler DG, Lin DT, McIntyre JF, Barker FG 2nd, Adams JA, Lopes VV, Varvares M, Loeffler JS, Chan AW. Proton beam radiation therapy for skull base adenoid cystic carcinoma. Arch Otolaryngol Head Neck Surg. 2006 Nov;132(11):1242-9.

Schulz-Ertner D, Nikoghosyan A, Jäkel O, Haberer T, Kraft G, Scholz M, Wannenmacher M, Debus J. Feasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas. Int J Radiat Oncol Biol Phys. 2003 Jun 1;56(2):391-8.

Schulz-Ertner D, Nikoghosyan A, Thilmann C, Haberer T, Jäkel O, Karger C, Kraft G, Wannenmacher M, Debus J. Results of carbon ion radiotherapy in 152 patients. Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):631-40.

Krempien R, Münter MW, Timke C, Friess H, Hartung G, Herfarth KK, et al. Cetuximab in combination with intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer: a prospective phase II trial [PARC-study ISRCTN56652283]. J Clin Oncol 2007; 25 (18S) 4573

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jensen AD, Nikoghosyan AV, Lossner K, Herfarth KK, Debus J, Münter MW. IMRT and carbon ion boost for malignant salivary gland tumors: interim analysis of the COSMIC trial. BMC Cancer. 2012 May 2;12:163.

Responsible Party:	PD Dr. MW Münter, Dept. of Radiation Oncology
ClinicalTrials.gov Identifier:	NCT01154270 History of Changes
Other Study ID Numbers:	COSMIC
Study First Received:	June 29, 2010
Last Updated:	April 23, 2013
Health Authority:	Germany: "Bundesamt für Strahlenschutz" (German Radiation Protection Authority)

Keywords provided by University of Heidelberg:

cancer of the salivary glands
radiation
carbon ion therapy

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 19, 2013