## Protocol Section
### Identification Module
**NCT ID:** NCT01182779

**Acronym:** HIT-1

**Brief Title:** Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base

**Official Title:** Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-

#### Organization Study ID Info
**ID:** HIT-1
#### Organization
**Class:** OTHER
**Full Name:** Heidelberg University
### Status Module
#### Completion Date
**Date:** 2023-08

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2010-08-17

**Type:** ESTIMATED

**Last Update Submit Date:** 2010-08-16

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2015-08

**Type:** ESTIMATED

#### Start Date
**Date:** 2010-07

**Status Verified Date:** 2010-07

#### Study First Post Date
**Date:** 2010-08-17
**Type:** ESTIMATED
**Study First Submit Date:** 2010-07-26
**Study First Submit QC Date:** 2010-08-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Heidelberg University

#### Responsible Party

**Old Name Title:** Juergen Debus, MD PhD, Dept. of Radiation Oncology, INF 400, 69120 Heidelberg

**Old Organization:** University of Heidelberg

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study is a prospective randomised clinical phase III trial. The primary objective of this study is to evaluate, if the innovative therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the local-progression free survival (LPFS).

**Detailed Description:** 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 skull base chordomas. 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 chordoma will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression free survival (LPFS) will be analysed as primary end point. Toxicity and survival are the secondary end points. Also matters of interest are patterns of recurrence, prognostic factors and plan quality.

### Conditions Module

**Conditions:**

- Chordoma

- Tumor

- Treatment

**Keywords:**

- base of skull chordoma

- radiation

- carbon ions

- protons

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 319

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E.

**Intervention Names:**

- Radiation: Carbon ion

**Label:** A

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Arm B (proton therapy):

Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4-6 days a week, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E.

**Intervention Names:**

- Radiation: Protons

**Label:** B

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- A

**Description:** 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 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E.

**Name:** Carbon ion

**Type:** RADIATION

#### Intervention 2

**Arm Group Labels:**

- B

**Description:** Arm B (proton therapy):

Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4-6 days a week, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E.

**Name:** Protons

**Type:** RADIATION

### Outcomes Module

#### Primary Outcomes

**Description:** The primary objective of this study is to evaluate, if the innovative therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the LPFS defined as time from the randomisation to observed local reccurrence or death from any cause in the absence of documented local disease progression. Lo-cal recurrence defined as MRT or CT - morphological tumor progress in the former irradiated region. A 10% increase in the LPFS is considered clinically relevant as-suming that the LPFS rate for the proton therapy is 70%.

**Measure:** local-progression free survival (LPFS)

**Time Frame:** 8-years

#### Secondary Outcomes

**Description:** Assessment of overall survival, progression free and metastasis free survival.

**Measure:** Survival

**Time Frame:** 8-years

**Description:** Local recurrences will be confirmed radiologically and histologically whenever possible. At least two medical doctors (radiation oncologist and/or radiologist) will be required to judge of the recurrence.

**Measure:** Local control and patterns of recurrence

**Time Frame:** 8 years

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

**Measure:** Toxicity

**Time Frame:** 8 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Karnofsky Performance Score ≥60%
* Age \>18 years and \<80 years
* Informed consent signed by the patient
* Histological confirmation of chordoma with infiltration of the skull base.

Exclusion Criteria:

* Inability to understand the aims of the study, no informed consent
* Prior RT of skull base region
* Other malignancies with disease-free interval \< 5 years (excepting pre- cancerous lesions)
* Participation in another trial
* Pregnancy
* Simultaneous CHT or Immunotherapy.

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** anna.nikoghosyan@med.uni-heidelberg.de

**Name:** Anna V. Nikoghosyan, MD

**Phone:** +496221568202

**Role:** CONTACT

**Contact 2:**

**Email:** juergen.debus@med.uni-heidelberg.de

**Name:** Juergen Debus, MD, PhD

**Phone:** +496221568202

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Heidelberg

**Contacts:**

***Contact 1:***

- **Name:** Juergen Debus, MD, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 2:***

- **Name:** Anna V. Nikoghosyan, MD

- **Role:** SUB_INVESTIGATOR

**Country:** Germany

**Facility:** University of Heidelberg

**Status:** RECRUITING

**Zip:** 69120

#### Overall Officials

**Official 1:**

**Affiliation:** Heidelberg University

**Name:** Juergen Debus, MD PhD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999 Jun;175 Suppl 2:57-63. doi: 10.1007/BF03038890.

**PMID:** 10394399

**Citation:** Ares C, Hug EB, Lomax AJ, Bolsi A, Timmermann B, Rutz HP, Schuller JC, Pedroni E, Goitein G. Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report. Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1111-8. doi: 10.1016/j.ijrobp.2008.12.055. Epub 2009 Apr 20.

**PMID:** 19386442

**Citation:** Hug EB. Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus. 2001 Mar 15;10(3):E11. doi: 10.3171/foc.2001.10.3.12.

**PMID:** 16734403

**Citation:** Hug EB, Slater JD. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. Neurosurg Clin N Am. 2000 Oct;11(4):627-38.

**PMID:** 11082173

**Citation:** Weber DC, Rutz HP, Pedroni ES, Bolsi A, Timmermann B, Verwey J, Lomax AJ, Goitein G. Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):401-9. doi: 10.1016/j.ijrobp.2005.02.023.

**PMID:** 16168833

**Citation:** Schulz-Ertner D, Karger CP, Feuerhake A, Nikoghosyan A, Combs SE, Jakel O, Edler L, Scholz M, Debus J. Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordomas. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):449-57. doi: 10.1016/j.ijrobp.2006.12.059. Epub 2007 Mar 23.

**PMID:** 17363188

**Citation:** Mizoe JE, Hasegawa A, Takagi R, Bessho H, Onda T, Tsujii H. Carbon ion radiotherapy for skull base chordoma. Skull Base. 2009 May;19(3):219-24. doi: 10.1055/s-0028-1114295.

**PMID:** 19881902

**Citation:** Nikoghosyan AV, Karapanagiotou-Schenkel I, Munter MW, Jensen AD, Combs SE, Debus J. Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base, clinical phase III study HIT-1-Study. BMC Cancer. 2010 Nov 5;10:607. doi: 10.1186/1471-2407-10-607.

**PMID:** 21054824

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M6057

- Name: Chordoma

- Relevance: HIGH

- As Found: Chordoma

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: T1175

- Name: Chordoma

- Relevance: HIGH

- As Found: Chordoma

### Condition Browse Module - Meshes

- ID: D000002817

- Term: Chordoma

### Misc Info Module

- Version Holder: 2024-05-24
