Intensity-Modulated or Proton Radiation Therapy for Sinonasal Malignancy

ID: NCT01586767
Status: Active, not recruiting
Phase: Phase 2
Start Date: July 01, 2011
First Submitted: October 21, 2011
Last Updated: February 13, 2018
Results: N/A
Sponsors & Collaborators: Massachusetts General Hospital, National Institutes of Health (NIH), National Cancer Institute (NCI)
Location: United States
Conditions: Adenoid Cystic Carcinoma, Squamous Cell Carcinoma, Sinonasal Carcinoma, Sinonasal Undifferentiated Carcinoma, Mucoepidermoid Carcinoma, Schneiderian Carcinoma, Myoepithelial Carcinoma, Esthesioneuroblastoma, Melanoma
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Study Description

Brief Summary

The purpose of this study is to test the hypothesis that 1)intensity-modulated radiotherapy (IMRT) or proton radiation therapy would result in improved local control rate and lowered toxicity compared to conventional radiotherapy, and 2) proton radiation therapy would result in equivalent or improved local control rate with similar or lower toxicity compared to IMRT, in the treatment of locally advanced sinonasal malignancy.

Data from retrospective studies suggest that IMRT or proton radiation therapy resulted in promising outcome in patients with sinonasal malignancy. To this date, no prospective study has been conducted to evaluate the outcome of sinonasal cancer treated with IMRT or proton radiation therapy. This Phase II trial is the first prospective study conducted to determine the treatment outcome and toxicity of IMRT or proton in the treatment of sinonasal cancer.

IMRT and proton radiation therapy are the two most established and most commonly employed advanced radiotherapy techniques for the treatment of sinonasal cancer. It is highly controversial whether one is superior to the other in terms of local control and toxicity outcome. It is also not clear if a subset of patients would benefit more from one treatment technology versus the other.

Due to the rarity and heterogeneity of sinonasal malignancies and the fact that proton beam is only available at a few centers in the United States, it is not feasible at present to do a Phase III study randomizing patients between IMRT and proton radiation therapy. In this study, a planned secondary analysis will be performed, comparing the treatment and toxicity outcome between IMRT and proton. The data on the IMRT and proton comparison from this trial will be used to design future multi-center prospective trials and to determine if randomized trial is necessary.

In this study, the treatment technique employed for an individual case will not be determined by the treating physician(s), but rather by the most advanced technology available at the treating institution for the treatment of the sinonasal cancer. At the Massachusetts General Hospital (MGH), proton beam therapy will be used for patients who meet the eligibility criteria. For institutions where protons are not available or institutions where the proton planning systems have not been optimized, IMRT exclusively will be used for the treatment of sinonasal cancer. Patient and tumor characteristics are expected to be comparable between IMRT- and proton- institutions

Detailed Description

Subjects will receive daily proton radiation treatment as outpatients at the Francis H. Burr Proton Center at Massachusetts General Hospital. The subjects may also receive concurrent standard chemotherapy every week during their radiation therapy. This chemotherapy is considered standard treatment for their cancer and is not being done for research purposes.

In addition to daily radiation treatments, subjects will have the following tests every week: review of side effects; physical exam, including weight, height, neurological exam and vital signs; and blood tests, only for those subjects also receiving chemotherapy.

Subjects will be followed for 5 years after the completion of study treatment. The first follow-up visit will be 6-8 weeks after completion of study treatment. Additional follow-up visits will be performed every 3 months during the first 2 years following completion of radiation then every 6 month during years 3-5. At each follow-up visit, subjects will receive a physical exam, chest CT scan (at 1st follow-up visit then at least every 6 months), a CT or MRI tumor assessment (at 1st follow-up visit then at least every 6 months), quality-of-life questionnaire, hearing test, neuro-ophthalmology test, and neurocognitive test.
Condition or disease Intervention/treatment Phase

Adenoid Cystic Carcinoma

Esthesioneuroblastoma

Melanoma

Mucoepidermoid Carcinoma

Myoepithelial Carcinoma

Schneiderian Carcinoma

Sinonasal Carcinoma

Sinonasal Undifferentiated Carcinoma

Squamous Cell Carcinoma

Radiation: Proton radiation therapy
Other Names
Radiation: Intensity-modulated radiotherapy
Other Names
IMRT
Phase 2

Tracking Information

First Submitted DateOctober 21, 2011
Last Update Posted DateFebruary 13, 2018
Start DateJuly 01, 2011
Anticipated Completion DateJuly 01, 2021
Primary Completion DateJuly 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Local Control Rates [Time Frame: 2 years]

    To determine the local control rates with IMRT or proton radiation therapy at 2 years.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Vision preservation [Time Frame: 5 years]

    To determine the late visual-orbital late effects of IMRT or proton beam

  • Regional control [Time Frame: 2 years]

    To determine the regional control at 2 years after IMRT or proton

  • Survival [Time Frame: 5 years]

    To determine the long-term survival at 5 years after IMRT or proton

  • QOL [Time Frame: 5 years]

    To assess quality-of-life (QOL) outcomes after IMRT or proton

  • Patterns of Tumor Relapse [Time Frame: 5 years]

    To determine the patterns of tumor relapse after IMRT or proton

  • Local control [Time Frame: 5 years]

    To determine long-term local control after IMRT or proton

  • Neurocognitive function [Time Frame: 5 years]

    To determine long-term neurocognitive function after IMRT or proton

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleIntensity-Modulated or Proton Radiation Therapy for Sinonasal Malignancy
Official TitleA Phase II Study of Intensity-Modulated or Proton Radiation Therapy for Locally Advanced Sinonasal Malignancy
Brief Summary

The purpose of this study is to test the hypothesis that 1)intensity-modulated radiotherapy (IMRT) or proton radiation therapy would result in improved local control rate and lowered toxicity compared to conventional radiotherapy, and 2) proton radiation therapy would result in equivalent or improved local control rate with similar or lower toxicity compared to IMRT, in the treatment of locally advanced sinonasal malignancy.

Data from retrospective studies suggest that IMRT or proton radiation therapy resulted in promising outcome in patients with sinonasal malignancy. To this date, no prospective study has been conducted to evaluate the outcome of sinonasal cancer treated with IMRT or proton radiation therapy. This Phase II trial is the first prospective study conducted to determine the treatment outcome and toxicity of IMRT or proton in the treatment of sinonasal cancer.

IMRT and proton radiation therapy are the two most established and most commonly employed advanced radiotherapy techniques for the treatment of sinonasal cancer. It is highly controversial whether one is superior to the other in terms of local control and toxicity outcome. It is also not clear if a subset of patients would benefit more from one treatment technology versus the other.

Due to the rarity and heterogeneity of sinonasal malignancies and the fact that proton beam is only available at a few centers in the United States, it is not feasible at present to do a Phase III study randomizing patients between IMRT and proton radiation therapy. In this study, a planned secondary analysis will be performed, comparing the treatment and toxicity outcome between IMRT and proton. The data on the IMRT and proton comparison from this trial will be used to design future multi-center prospective trials and to determine if randomized trial is necessary.

In this study, the treatment technique employed for an individual case will not be determined by the treating physician(s), but rather by the most advanced technology available at the treating institution for the treatment of the sinonasal cancer. At the Massachusetts General Hospital (MGH), proton beam therapy will be used for patients who meet the eligibility criteria. For institutions where protons are not available or institutions where the proton planning systems have not been optimized, IMRT exclusively will be used for the treatment of sinonasal cancer. Patient and tumor characteristics are expected to be comparable between IMRT- and proton- institutions

Detailed Description

Subjects will receive daily proton radiation treatment as outpatients at the Francis H. Burr Proton Center at Massachusetts General Hospital. The subjects may also receive concurrent standard chemotherapy every week during their radiation therapy. This chemotherapy is considered standard treatment for their cancer and is not being done for research purposes.

In addition to daily radiation treatments, subjects will have the following tests every week: review of side effects; physical exam, including weight, height, neurological exam and vital signs; and blood tests, only for those subjects also receiving chemotherapy.

Subjects will be followed for 5 years after the completion of study treatment. The first follow-up visit will be 6-8 weeks after completion of study treatment. Additional follow-up visits will be performed every 3 months during the first 2 years following completion of radiation then every 6 month during years 3-5. At each follow-up visit, subjects will receive a physical exam, chest CT scan (at 1st follow-up visit then at least every 6 months), a CT or MRI tumor assessment (at 1st follow-up visit then at least every 6 months), quality-of-life questionnaire, hearing test, neuro-ophthalmology test, and neurocognitive test.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
39
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Adenoid Cystic Carcinoma
Esthesioneuroblastoma
Melanoma
Mucoepidermoid Carcinoma
Myoepithelial Carcinoma
Schneiderian Carcinoma
Sinonasal Carcinoma
Sinonasal Undifferentiated Carcinoma
Squamous Cell Carcinoma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Radiation: Proton radiation therapy

Daily proton radiation therapy

Other Names
Radiation: Intensity-modulated radiotherapy

Daily intensity-modulated radiotherapy

Other Names
IMRT
Study Groups/Cohorts
Proton beam therapy
Subjects treated at Massachusetts General Hospital with proton beam therapy

IMRT
Intensity-modulated radiation therapy at institutions other than Massachusetts General Hospital

Study Arms
Active Comparator IMRT
Intensity-modulated radiation therapy at institutions other than Massachusetts General Hospital
Radiation : Intensity-modulated radiotherapy
Daily intensity-modulated radiotherapy

Active Comparator Proton beam therapy
Subjects treated at Massachusetts General Hospital with proton beam therapy
Radiation : Proton radiation therapy
Daily proton radiation therapy

Arm Intervention/Treatment
Active Comparator IMRT
Intensity-modulated radiation therapy at institutions other than Massachusetts General Hospital
Radiation : Intensity-modulated radiotherapy
Active Comparator Proton beam therapy
Subjects treated at Massachusetts General Hospital with proton beam therapy
Radiation : Proton radiation therapy

Recruitment Information

Recruitment Status:Active, not recruiting
Enrollment39
Completion DateJuly 01, 2021
Eligibility Criteria: Inclusion Criteria:
- Biopsy proven, within 16 weeks prior to study entry, sinonasal adenoid cystic carcinoma, adenocarcinoma, mucoepidermoid carcinoma, squamous cell carcinoma, including sinonasal carcinoma, sinonasal undifferentiated carcinoma, Schneiderian carcinoma, myoepithelial carcinoma, undifferentiated carcinoma, esthesioneuroblastoma, or melanoma AJCC 7th edition Stage III - IVA/B tumors, or with skull base or intracranial extension. Pathology must be confirmed by review at the treating institution.
- Patients with biopsy proven locally advanced sinus, nasal cavity, hard palate, soft palate, major or minor salivary gland tumors, or lacrimal apparatus, with nasal cavity, sinus, auditory canal, or skull base involvement are eligible.
- Eastern cooperative oncology group (ECOG) performance status 0 - 1 or Karnofsky Performance Status ≥ 70. (Appendix B)
- All patients must undergo pre-treatment evaluation of tumor extent prior to study entry through imaging studies and clinical examinations, including CT and/or MRI of skull base, brain and neck within 28 days prior to study entry; physical examination +/- nasal endoscopy within 28 days prior to study entry; and CT of the chest within 60 days prior to study entry.
- Nutritional and general physical condition must be considered compatible with the proposed radiation +/- chemotherapy treatment.
- Normal organ and marrow function

Exclusion Criteria:
- Active alcohol addiction
- Pregnant or breastfeeding
- Receiving any other study agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin for subjects who will receive chemotherapy
- Evidence of distant metastases or distant leptomeningeal metastases
- Previous irradiation for head and neck tumor, skull base, or brain tumors
- Uncontrolled intercurrent illness
- History of a different malignancy unless disease-free for at least 2 years and are deemed by the investigator to be at low-risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated for cure within the past 2 years: cervical cancer in situ, carcinoma in situ of the breast, and basal cell or squamous ceel carcinoma of the skin
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT01586767
Other Study ID Numbers
10-308
2P01CA021239-29
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyAnnie W. Chan, MD, Massachusetts General Hospital
Study Sponsor
Massachusetts General Hospital
Collaborators
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Principal Investigator
Annie W Chan, MD
Massachusetts General Hospital