Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Nasopharyngeal Carcinoma

Recurrence

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Treated with carcon ion radiotherapy along with concurrent chemotherapy (Cisplatin 40mg/m\^2, weekly).

Five dose levels (52.5GyE, 55GyE, 57.5GyE, 60GyE, 62.5GyE) are planned within the Phase I part. Daily fraction of 2.5 GyE will be delivered for all dose levels. After the recommended dose (RD), i.e., MTD, is determined or if the treatments to 62.5 GyE are safely delivered, the recommended dose (or 62.5 GyE) will be the prescribed dose in the Phase II part of the study. Ninety-five percent (95%) of the isodose line should cover the GTV+3\~5mm.

Carbon ion radiotherapy (CIRT)

Cisplatin (40mg/m\^2) monotherapy will be given weekly along with radiotherapy.

Jiade J Lu, MD

The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) along with concurrent chemotherapy in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD. Participants will be treated with CIRT with escalating dose regimens along with concurrent chemotherapy (40 mg/m\^2, weekly) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of concurrent chemoradiotherapy. Once the MTD for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial.

The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) along with concurrent chemotherapy in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD in the setting of concurrent chemoradiotherapy. Participants will be treated with CIRT with escalating dose starting from 52.5GyE (2.5GyE/daily fraction) to potentially 62.5GyE (2.5GyE/daily fraction) along with concurrent chemotherapy (40 mg/m\^2, weekly) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of concurrent chemoradiotherapy. Time-to-event continual reassessment method (TITE-CRM) is used for the phase I dose escalating part of the trial and approximately 25 patients will be accrued. Once the MTD in the setting of concurrent chemoradiotherapy for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial. The Phase II part of the trial will be a single phase single arm study.

Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma

Phase I/II Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

Shanghai Proton and Heavy Ion Center

Chordoma

Neoplasms, Germ Cell and Embryonal

Treatment is performed using 16 x 4 GyE protons

protons

Treatment is performed using 16 x 4 GyE carbon ions

carbon ions

The purpose of this study is to evaluate the safety and feasibility of primary hypofractionated irradiation of sacrococcygeal chordoma with carbon ions or protons using the raster scan technique.

The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococcygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points.

Ion Irradiation of Sacrococcygeal Chordoma

Hypofractionated Ion Irradiation (Protons or Carbon Ions) of Sacrococcygeal Chordoma

The evaluation is based on incidence of Grade 3-5 toxicity (NCI-CTC-AE) and/or discontinuation of the treatment for any reason. Endpoint is the proportion of treatments without Grade 3-5 toxicity (NCI-CTC-AE) up to 12 months after treatment and/or discontinuation of the treatment for any reason

local progression free survival (LPFS) is determined from start of treatment until local progression in imaging (\>10% size increase)

Further objectives are overall survival (OS) from date of treatment start until the date of death from any cause assessed up to 12 months

Quality of life (QoL) evaluated with EORTC-QLQ30 questionnaire.

Heidelberg University

Prof. Dr.

Carcinoma, Adenoid Cystic

Adenocarcinoma

Adenoid Cystic Carcinoma

Cetuximab

Antineoplastic Agents, Immunological

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

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

Alexandra D Jensen, MD MSc

Marc W Münter, MD

Aleandra D Jensen, MD MSc

Jürgen Debus, Prof. Dr. Dr.

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

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.

Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Combined Treatment of Adenoid Cystic Carcinoma With Cetuximab and IMRT Plus C12 Heavy Ion Boost - ACCEPT - (ACC, Erbitux, and Particle Therapy); Phase I/II Feasibility Study

The primary objective is to explore the toxicity of the combined treatment consisting of heavy ion therapy / IMRT and cetuximab by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4.

Acute treatment effects will be evaluated 6 weeks and late effects 3 years post completion of treatment

Local relapse-free survival will be defined as the time from the initial dose of study therapy to the time of locoregional disease progression or relapse or death, or to the date of last assessment without any such event (censored observation)

Distant relapse-free survival will be defined as the time from the initial dose of study therapy to the time of distant metastasis detection or death, or to the date of last assessment without any such event (censored observation)

Distant disease-free survival will be defined as the time from the initial dose of study therapy to the time of any detection of adenoid cystic carcinoma relapse or development of secondary cancer or death, or to the date of last assessment without any such event (censored observation)

The duration of survival will be determined by measuring the time interval from initial dose of study therapy to the date of death of any cause or last observation (censored)

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

University Hospital Heidelberg

Merck KGaA, Darmstadt, Germany

Prof. Dr. Dr. J. Debus

Salivary Gland Neoplasms

(8 x 3 GyE) carbon ion therapy followed by 50 Gy IMRT (2 Gy/ Fx)corresponding to a total dose of approximately 74 GyE.

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

carbon ion boost

Marc W Muenter, MD

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).

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)

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

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

to evaluate local control at 3 years post RT

evaluation of acute radiation effects (other than mucositis CTC°C) 6-8 weeks post completion of treatment

to evaluate disease-free survival at 3 years post radiotherapy

PD Dr. MW Münter

Carcinoma, Squamous Cell

Neoplasms, Squamous Cell

Juergen Debus, MD PhD

The IMRT-HIT-SNT 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, overall survival, and toxicity. Planned accrual of the trial includes 36 patients with histologically proven (≥R1-resected or inoperable) sinonasal malignancies.

Local control in sinonasal malignancies is dose dependent. However, dose escalation at acceptable toxicity is technically demanding even with modern radiotherapy techniques. Raster-scanned carbon ion therapy with highly conformal dose distributions may allow higher doses at comparable or reduced side-effects.

Methods/ design:

The IMRT-HIT-SNT 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 36 patients with histologically proven (≥R1-resected or inoperable) adeno-/ or squamous cell carcinoma of the nasal cavity or paransal sinuses. 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, overall survival, and toxicity (incl. mucositis CTC °I-II and late toxicity at 2 years post RT)are secondary endpoints.

Treatment of Malignant Sinonasal Tumours With Intensity-modulated Radiotherapy (IMRT) and Carbon Ion Boost (C12)

Incidence of mucositis ≥ CTC°III will be assessed as the primary endpoint of the trial at completion of radiation therapy

Investigator

Skin and Connective Tissue Diseases

Chondrosarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

Arm A (carbon ion therapy):

Total dose to the PTV2 - 45 Gy E in 3 Gy E /d, 4 - 6 days a week, 15 fractions Total dose to the PTV1 - 60 Gy E ± 5%, further 4 - 6 fractions a 3 Gy E.

Arm B (proton therapy):

Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4 - 6 days a week, 25 - 28 fractions Total dose to the PTV1 - 70 Gy E ± 5%, further 6 - 10 fractions a 2 Gy E.

carbon ion therapy

proton therapy

Anna V. Nikoghosyan, MD

Juergen Debus, MD, PhD

Rebecca Klumpp

The study is a prospective randomised clinical phase III trial. Proton therapy is the gold standard in the treatment of low and intermediate grad chondrosarcomas of the skull base. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Up until now it was impossible to compare two different particle therapies, i.e. proton and carbon ion therapy directly with each other. The aim of this study is to find out, whether the biological advantages of carbon ion therapy mentioned above can also be clinically confirmed.

The study is a prospective randomised clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.

Proton therapy is the gold standard in the treatment of low and intermediate grad chondrosarcomas of the skull base. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Up until now it was impossible to compare two different particle therapies, i.e. proton and carbon ion therapy directly with each other. The aim of this study is to find out, whether the biological advantages of carbon ion therapy mentioned above can also be clinically confirmed.

Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Plan quality is also a matter of interest.

Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base

Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base, Clinical Phase III Study

The primary objective of this study is to evaluate, if the innovative carbon ion therapy in chondrosarcomas is not relevantly inferior to the standard proton treatment with respect to the 5 year LPFS rate defined as time from the randomisation to observed local reccurrence. It is assumed that the LPFS rate for the proton therapy is 90%.

Assessment of overall survival, progression free and metastasis free survival.

Acute and late toxicity will be analysed according to Common Terminology Criteria for Adverse Events: CTCAE V4.0 for acute side effects and RTOG/EORTC for late reaction.

Local recurrences will be confirmed radiologically and histologically whenever possi-ble. At least two medical doctors (radiation oncologist and/or radiologist) will be re-quired to judge of the recurrence.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma	NCT02801487	Nasopharyngeal ...	Carbon ion radi... Cisplatin	18 Years - 70 Years	Shanghai Proton and Heavy Ion Center
Ion Irradiation of Sacrococcygeal Chordoma	NCT01811394	Sacral Chordoma	protons carbon ions	18 Years - 80 Years	Heidelberg University
Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy	NCT01192087	Adenoid Cystic ...	Cetuximab	18 Years - 70 Years	Heidelberg University
Ion Irradiation of Sacrococcygeal Chordoma	NCT01811394	Sacral Chordoma	protons carbon ions	18 Years - 80 Years	Heidelberg University
CO(Mbined Therapy of Malignant) S(Alivary Gland tu)M(Ours With)I(MRT and) c(Arbon Ions): COSMIC	NCT01154270	Malignancy Salivary Glands Tumor	carbon ion boos...	18 Years - 80 Years	Heidelberg University
Treatment of Malignant Sinonasal Tumours With Intensity-modulated Radiotherapy (IMRT) and Carbon Ion Boost (C12)	NCT01220752	Sinonasal Malig... Adenocarcinoma ...	carbon ion boos...	18 Years - 80 Years	Heidelberg University
Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base	NCT01182753	Chondrosarcoma	carbon ion ther... proton therapy	18 Years - 80 Years	Heidelberg University
Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma	NCT02801487	Nasopharyngeal ...	Carbon ion radi... Cisplatin	18 Years - 70 Years	Shanghai Proton and Heavy Ion Center

Spots Global Cancer Trial Database for carbon ion therapy