Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

NCT ID: NCT01192087

Last Updated: 2013-04-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2017-07-31

Brief Summary

The ACCEPT (A(denoid) c(ystic) c(arcinoma), E(rbitux, and) p(article) t(herapy))-trial is a prospective, monocentric phase I/II feasibility trial evaluating toxicity and efficacy in the combined treatment of intensity-modulated radiation therapy (IMRT) and carbon ion (C12) boost with the epidermal growth factor receptor (EGFR) antibody cetuximab. The primary objective of the study is to explore the toxicity of the combined modality regimen consisting of heavy ion therapy / IMRT and EGFR antibody immunotherapy, by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4. Secondary endpoints include local control, distant control, overall disease-free survival, overall survival

Detailed Description

Treatment with novel radiotherapeutic technologies could increase local control in adenoid cystic carcinoma of the head and neck. Especially combined treatment with intensity-modulated radiation therapy and heavy ion (C12) boost to the primary tumor or previous tumor bed could be established as the treatment of choice in this disease.

Unfortunately, therapeutic results in the treatment of adenoid cystic carcinoma are still hampered by the occurrence of distant metastases (predominantly in the lungs) which, though progressing comparatively slowly, still limit the patient's life expectancy. Most adenoid cystic carcinomas (> 80%) though, exhibit over-expression of EGFR receptors and hence provide an approach for systemic treatment. In this prospective phase II trial, the application of the EGFR antibody cetuximab will be evaluated in combination with the established treatment of intensity-modulated radiation therapy plus C12 heavy ion boost.

The trial aims at evaluation of toxicity and feasibility of the combined treatment, as primary endpoint, as well as local control and disease-free survival as secondary endpoints.

Conditions

Adenoid Cystic Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab arm

patients receive weekly cetuximab in combination with IMRT and carbon ion boost

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

cetuximab initial dose (7 days prior to RT treatment start): 400 mg/m² body surface cetuximab weekly doses (from RT treatment start throughout radiation treatment): 250 mg/m² body surface

Interventions

Cetuximab

cetuximab initial dose (7 days prior to RT treatment start): 400 mg/m² body surface cetuximab weekly doses (from RT treatment start throughout radiation treatment): 250 mg/m² body surface

Intervention Type: DRUG

Other Intervention Names

Cetuximab (Erbitux)

Eligibility Criteria

Inclusion Criteria

• Histologically proven, or surgically resected adenoid-cystic carcinoma of the head and neck and
• macroscopic or microscopic residual tumor (R1/ R2) or
• Tumor stage >T3/T4 or
• perineural invasion and
• M0 stage
• Written informed consent
• Age between 18 and 70 years
• Karnofsky Index ≥ 70%
• Adequate bone-marrow, liver, and kidney function:
• neutrophils ≥ 1.5 x 109/L,
• thrombocytes ≥ 100 x 109/L,
• haemoglobin ≥ 10.0 g/dL
• bilirubin ≤ 2.0 g/dL
• SGOT, SGPT, AP, gamma-GT ≤ 3 x ULN
• serum creatinine ≤ 1.5 mg/dL
• effective contraception

Exclusion Criteria

• Prior RT or chemotherapy for tumors of the head and neck
• R0 resection
• M1 (distant metastases)
• prior immunotherapy
• signs of active infection
• other serious illnesses
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
• Significant neurologic or psychiatric disorders including dementia or seizures
• Active disseminated intravascular coagulopathies
• Other serious underlying medical conditions prohibiting the patient's participation in the trial according to the judgement of the investigators
• Active participation in another clinical trial within the past 30 days
• Known allergic/ hypersensitivity reactions to non-human proteins
• Women: pregnant (Positive serum/ urine beta-HCG ) or breast-feeding,
• Known drug abuse,
• Other previous malignancy within the past 5 years, with exception of a history of a previous, adequately treated, basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix,
• Legal incapacity or limited legal capacity,
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

UNKNOWN

Sponsor Role: collaborator

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

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

Principal Investigators

Jürgen Debus, Prof. Dr. Dr.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Dept. of Radiation Oncology

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Alexandra D Jensen, MD MSc

Role: CONTACT

alexandra.jensen@med.uni-heidelberg.de

+49-6221-56- ext. 8202

Marc W Münter, MD

Role: CONTACT

marc.muenter@med.uni-heidelberg.de

+49-6221-56- ext. 8202

Facility Contacts

Aleandra D Jensen, MD MSc

Role: primary

alexandra.jensen@med.uni-heidelberg.de

+49-6221-56 ext. 8202

References

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. doi: 10.1016/j.ijrobp.2006.04.014.

Reference Type: BACKGROUND

PMID: 16904520 (View on PubMed)

Munter 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. doi: 10.1186/1748-717X-1-17.

Reference Type: BACKGROUND

PMID: 16756669 (View on PubMed)

Schulz-Ertner D, Nikoghosyan A, Didinger B, Munter M, Jakel 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. doi: 10.1002/cncr.21158.

Reference Type: BACKGROUND

PMID: 15937907 (View on PubMed)

Schulz-Ertner D, Nikoghosyan A, Thilmann C, Haberer T, Jakel 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. doi: 10.1016/j.ijrobp.2003.09.041.

Reference Type: BACKGROUND

PMID: 14751537 (View on PubMed)

Schulz-Ertner D, Nikoghosyan A, Jakel 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. doi: 10.1016/s0360-3016(02)04511-x.

Reference Type: BACKGROUND

PMID: 12738314 (View on PubMed)

Jakel O, Kramer M, Schulz-Ertner D, Heeg P, Karger CP, Didinger B, Nikoghosyan A, Debus J. Treatment planning for carbon ion radiotherapy in Germany: review of clinical trials and treatment planning studies. Radiother Oncol. 2004 Dec;73 Suppl 2:S86-91. doi: 10.1016/s0167-8140(04)80022-7.

Reference Type: BACKGROUND

PMID: 15971317 (View on PubMed)

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. doi: 10.1016/s0167-8140(00)00273-5.

Reference Type: BACKGROUND

PMID: 11325445 (View on PubMed)

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. doi: 10.1001/archotol.129.9.944.

Reference Type: BACKGROUND

PMID: 12975266 (View on PubMed)

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. doi: 10.1001/archotol.132.11.1242.

Reference Type: BACKGROUND

PMID: 17116822 (View on PubMed)

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. doi: 10.1016/j.ijrobp.2004.02.067.

Reference Type: BACKGROUND

PMID: 15380567 (View on PubMed)

de Haan LD, De Mulder PH, Vermorken JB, Schornagel JH, Vermey A, Verweij J. Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck. Head Neck. 1992 Jul-Aug;14(4):273-7. doi: 10.1002/hed.2880140403.

Reference Type: BACKGROUND

PMID: 1381339 (View on PubMed)

Kaplan MJ, Johns ME, Cantrell RW. Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg. 1986 Sep;95(2):165-70. doi: 10.1177/019459988609500206.

Reference Type: BACKGROUND

PMID: 3035459 (View on PubMed)

Suen JY, Johns ME. Chemotherapy for salivary gland cancer. Laryngoscope. 1982 Mar;92(3):235-9. doi: 10.1288/00005537-198203000-00003.

Reference Type: BACKGROUND

PMID: 6279995 (View on PubMed)

Creagan ET, Woods JE, Rubin J, Schaid DJ. Cisplatin-based chemotherapy for neoplasms arising from salivary glands and contiguous structures in the head and neck. Cancer. 1988 Dec 1;62(11):2313-9. doi: 10.1002/1097-0142(19881201)62:113.0.co;2-4.

Reference Type: BACKGROUND

PMID: 3179947 (View on PubMed)

Dreyfuss AI, Clark JR, Fallon BG, Posner MR, Norris CM Jr, Miller D. Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin. Cancer. 1987 Dec 15;60(12):2869-72. doi: 10.1002/1097-0142(19871215)60:123.0.co;2-y.

Reference Type: BACKGROUND

PMID: 2824016 (View on PubMed)

Venook AP, Tseng A Jr, Meyers FJ, Silverberg I, Boles R, Fu KK, Jacobs CD. Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group. J Clin Oncol. 1987 Jun;5(6):951-5. doi: 10.1200/JCO.1987.5.6.951.

Reference Type: BACKGROUND

PMID: 3585449 (View on PubMed)

Laurie SA, Licitra L. Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006 Jun 10;24(17):2673-8. doi: 10.1200/JCO.2005.05.3025.

Reference Type: BACKGROUND

PMID: 16763282 (View on PubMed)

Dodd RL, Slevin NJ. Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol. 2006 Sep;42(8):759-69. doi: 10.1016/j.oraloncology.2006.01.001. Epub 2006 Jun 6.

Reference Type: BACKGROUND

PMID: 16757203 (View on PubMed)

Airoldi M, Gabriele AM, Gabriele P, Pedani F, Marchionatti S, Succo G, Beatrice F, Bumma C. Concomitant chemoradiotherapy followed by adjuvant chemotherapy in parotid gland undifferentiated carcinoma. Tumori. 2001 Jan-Feb;87(1):14-7. doi: 10.1177/030089160108700103.

Reference Type: BACKGROUND

PMID: 11669550 (View on PubMed)

Haddad RI, Posner MR, Busse PM, Norris CM Jr, Goguen LA, Wirth LJ, Blinder R, Krane JF, Tishler RB. Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ sparing approach. Am J Clin Oncol. 2006 Apr;29(2):153-7. doi: 10.1097/01.coc.0000203756.36866.17.

Reference Type: BACKGROUND

PMID: 16601434 (View on PubMed)

Younes MN, Park YW, Yazici YD, Gu M, Santillan AA, Nong X, Kim S, Jasser SA, El-Naggar AK, Myers JN. Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther. 2006 Nov;5(11):2696-705. doi: 10.1158/1535-7163.MCT-05-0228.

Reference Type: BACKGROUND

PMID: 17121916 (View on PubMed)

Vered M, Braunstein E, Buchner A. Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland origin. Head Neck. 2002 Jul;24(7):632-6. doi: 10.1002/hed.10104.

Reference Type: BACKGROUND

PMID: 12112535 (View on PubMed)

Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL. Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol. 2005 Jan 20;23(3):585-90. doi: 10.1200/JCO.2005.06.125.

Reference Type: BACKGROUND

PMID: 15659505 (View on PubMed)

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. doi: 10.1056/NEJMoa053422.

Reference Type: BACKGROUND

PMID: 16467544 (View on PubMed)

Alcedo JC, Fabrega JM, Arosemena JR, Urrutia A. Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases. Head Neck. 2004 Sep;26(9):829-31. doi: 10.1002/hed.20094.

Reference Type: BACKGROUND

PMID: 15350030 (View on PubMed)

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. doi: 10.1093/jnci/92.3.205.

Reference Type: BACKGROUND

PMID: 10655437 (View on PubMed)

Adeberg S, Akbaba S, Lang K, Held T, Verma V, Nikoghosyan A, Bernhardt D, Munter M, Freier K, Plinkert P, Hauswald H, Herfarth K, Rieken S, Debus J, Jensen AD. The Phase 1/2 ACCEPT Trial: Concurrent Cetuximab and Intensity Modulated Radiation Therapy with Carbon Ion Boost for Adenoid Cystic Carcinoma of the Head and Neck. Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):167-173. doi: 10.1016/j.ijrobp.2019.09.036. Epub 2019 Oct 3.

Reference Type: DERIVED

PMID: 31586664 (View on PubMed)

Jensen AD, Nikoghosyan A, Hinke A, Debus J, Munter MW. Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux(R) and particle therapy]. BMC Cancer. 2011 Feb 15;11:70. doi: 10.1186/1471-2407-11-70.

Reference Type: DERIVED

PMID: 21320355 (View on PubMed)

Other Identifiers

ACCEPT

Identifier Type: -

Identifier Source: org_study_id