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

Tumor Clinical Trial

— COSMIC  

Official title:

Combined Therapy of Malignant Salivary Gland Tumours With IMRT and Carbon Ions: COSMIC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01154270
• Other study ID #: COSMIC
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 29, 2010
• Last updated: April 23, 2013
• Start date: June 2010
• Est. completion date: September 2013

Study information

• Verified date: April 2013
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: "Bundesamt für Strahlenschutz" (German Radiation Protection Authority)
• Study type: Interventional

Clinical Trial Summary

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).

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: September 2013
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Malignancy
• Salivary Glands
• Tumor

Intervention

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

Locations

Country	Name	City	State
Germany	Dept. of Radiation Oncology, INF 400	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Country where clinical trial is conducted

Germany, 

References & Publications (20)

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. doi: 10.1016/j.ijrobp.2008.01.016. Epub 2008 Apr 18. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Münter M, Umathum V, Nikoghosyan A, Jensen A, Hof H, Jaekel O, et al. Combination of intensity modulated radiation therapy (IMRT) and a carbon ion boost for subtotal resected or inoperable adenoid cystic carcinomas (ACC's) of the head and neck. PTCOG meeting 2009, abstract FC84

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mucositis = CTC°3		6-8 weeks post completion of treatment	Yes
Secondary	local control	to evaluate local control at 3 years post RT	3 years post RT	No
Secondary	acute toxicity	evaluation of acute radiation effects (other than mucositis CTC°C) 6-8 weeks post completion of treatment	6-8 weeks post completion of treatment	Yes
Secondary	late toxicity	to evaluate radiation late effects	3 years post radiotherapy	Yes
Secondary	disease-free survival	to evaluate disease-free survival at 3 years post radiotherapy	3 years post treatment	No