Proton Radiation for Lymphoma Involving Mediastinum

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01751412
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 48
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This research study is a Pilot Study. Pilot studies are conducted to see if it is practical to do this type of research on a larger scale in the future. The pilot part of this study is to assess the possibility of using proton radiation to treat lymphomas. Proton radiation is used for many other types of malignancies, but its use for the treatment of lymphoma has been limited. The treatment is still being studied as research doctors are trying to find out more about its use in the treatment of different types of lymphoma. Proton beam radiation therapy is an FDA approved radiation delivery system.

Patients are being asked to participate in this research study if they have lymphoma in the center of their chest, near their heart. Conventional radiation therapy with photons is used as standard treatment for many patients with lymphoma. In this research study investigators are looking at another type of radiation called proton radiation, which is known to spare surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area requiring radiation but delivers no dose beyond the region requiring treatment. This may reduce side effects that patients would normally experience with conventional radiation therapy or other means of delivering proton radiation therapy.

In this research study, investigators are evaluating the effectiveness of using proton radiation delivered to reduce side effects associated with radiation treatment.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Radiation: Proton Radiation	N/A

Detailed Description

If a person agrees to participate in this research study, they will be asked to undergo some screening tests or procedures to confirm eligibility. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that a patient does not take part in the research study. If a patient has had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, performance status, physical examination, assessment of tumor, echocardiogram, electrocardiogram, pulmonary (lung) function tests and blood tests. If these tests show that a patient is eligible to participate in the research study, they will begin the study treatment. If a patient does not meet the eligibility criteria, they will not be able to participate in the research study.

Proton radiation will be delivered daily for 2 to 5 weeks, depending on the dose prescribed by your physician. Treatment is delivered (Monday-Friday) for 5 days (no weekends or holidays). Each treatment will require that you lie on a table for 30 to 45 minutes.

Participants will receive radiation therapy as an outpatient at Massachusetts General Hospital. During radiation therapy, they will have the following weekly assessments and procedures: physical exam, assess for any side effects, blood tests for cardiac markers.

Study participants will be asked to return for a follow up visit 6-12 weeks after their last dose of radiation therapy. During this visit the following tests and procedures will be done: PET/CT scan, physical exam, assess for side effects and blood tests for cardiac markers.

Participants will also be asked to return for a follow-up visit at 6 months, 12 months and annually for five years post radiation. Keeping in touch with study participants and checking on their condition helps investigators look at the long-term effects of the research study. At these visits, the following tests and procedures will be done: physical exam, assess for any side effects, ECG, ECHO, pulmonary tests, PET/CT scan, routine blood tests and blood tests for cardiac markers (at 6 months and 1 years only).

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study Evaluating the Use of Proton Radiation for Treatment of Lymphoma Involving the Mediastinum
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Proton Radiation Delivered daily (Monday-Friday) for two to five weeks.	Radiation: Proton Radiation

Outcome Measures

Primary Outcome Measures

1. Mean Radiation Dose to Normal Heart Tissue [6 weeks]

   The mean radiation dose to the heart in Gy RBE (Gray relative biological effectiveness).

2. Radiation Dose to the Normal Tissue of the Lungs [6 Weeks]

   The percentage of the lung volume which received radiation dose of 20 Gray (Gy) or more. The lung volume percentages for the 12 participants were averaged and presented separately for the left and right lungs.

Secondary Outcome Measures

1. Local Control [2 years]

   The number of participants who maintained local control for the duration of their followup. Local control is defined as the lack of disease progression. Progression is the increased growth of cancer cells or the spread of the cancer cells to another location within the body.

2. Number of Participants With Acute Toxicities [90 Days]

   Acute toxicities including pericarditis, pneumonitis, Lhermitte's, dermatitis, mucositis, esophagitis, leukopenia, xerostomia, and thrombocytopenia. Data is shown as the number of participants that experienced the given toxicities.

3. Late Toxicities [5 years]

   Late toxicities including clinical and sub-clinical heart disease, pulmonary fibrosis, esophageal stricture, myelopathy, thyroid dysfunction and secondary cancers.

4. 6-Month Overall Survival [6 Months]

   The number of participants surviving six months after starting treatment

5. 6-Month Progression-Free Survival [6 Months]

   The number of participants surviving without disease progression six months after the start of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed Hodgkin lymphoma or non-Hodgkin lymphoma

• Must complete standard chemotherapy appropriate for the histologic subtype of lymphoma and be able to start radiation therapy within 3-6 weeks of completing chemotherapy

• Life expectancy of at least 12 months

• Must have achieved complete or partial response per appropriate imaging technique within 4 weeks of study entry following administration of chemotherapy

• Individuals with known history of HIV positivity must be on appropriate HAART therapy

Exclusion Criteria:

• Pregnant or breastfeeding

• Prior therapeutic radiation therapy > 200 cGy has been delivered to target volume

• Have not recovered from adverse events due to systemic agents administered more than 4 weeks earlier

• Uncontrolled intercurrent illness

• History of a different malignancy unless disease free for at least 2 years (cervical cancer in situ, basal or squamous cell carcinoma are acceptable)

• Receiving any other investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Thomas DeLaney, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tom DeLaney, MD, Medical Director, Francis H. Burr Proton Therapy Center, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01751412
• Other Study ID Numbers: 12-346
• First Posted: Dec 18, 2012
• Last Update Posted: Nov 24, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Tom DeLaney, MD, Medical Director, Francis H. Burr Proton Therapy Center, Massachusetts General Hospital: Hodgkin; Non-Hodgkin Lymphoma; Mediastinal; Adult Lymphoma; Pediatric Lymphoma
• Additional relevant MeSH terms: Lymphoma

Study Results

Participant Flow

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Overall Participants	12
Age (Count of Participants)
<=18 years	1 8.3%
Between 18 and 65 years	11 91.7%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	28
Sex: Female, Male (Count of Participants)
Female	10 83.3%
Male	2 16.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 91.7%
Unknown or Not Reported	1 8.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Mean Radiation Dose to Normal Heart Tissue
Description	The mean radiation dose to the heart in Gy RBE (Gray relative biological effectiveness).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
Mean (Full Range) [Gy(RBE)]	5.4

2. Primary Outcome

Title	Radiation Dose to the Normal Tissue of the Lungs
Description	The percentage of the lung volume which received radiation dose of 20 Gray (Gy) or more. The lung volume percentages for the 12 participants were averaged and presented separately for the left and right lungs.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
Left Lung	9.17
Right Lung	8.79

3. Secondary Outcome

Title	Local Control
Description	The number of participants who maintained local control for the duration of their followup. Local control is defined as the lack of disease progression. Progression is the increased growth of cancer cells or the spread of the cancer cells to another location within the body.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
Count of Participants [Participants]	10 83.3%

4. Secondary Outcome

Title	Number of Participants With Acute Toxicities
Description	Acute toxicities including pericarditis, pneumonitis, Lhermitte's, dermatitis, mucositis, esophagitis, leukopenia, xerostomia, and thrombocytopenia. Data is shown as the number of participants that experienced the given toxicities.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
pericarditis	0 0%
pneumonitis	0 0%
Lhermitte's	0 0%
dermatitis	9 75%
mucositis	0 0%
esophagitis	2 16.7%
leukopenia	0 0%
xerostomia	0 0%
thrombocytopenia	0 0%

5. Secondary Outcome

Title	Late Toxicities
Description	Late toxicities including clinical and sub-clinical heart disease, pulmonary fibrosis, esophageal stricture, myelopathy, thyroid dysfunction and secondary cancers.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The trial was terminated before the study endpoint was met. The data is not available for analysis.

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	0

6. Secondary Outcome

Title	6-Month Overall Survival
Description	The number of participants surviving six months after starting treatment
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
Count of Participants [Participants]	12 100%

7. Secondary Outcome

Title	6-Month Progression-Free Survival
Description	The number of participants surviving without disease progression six months after the start of treatment
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
Measure Participants	12
Count of Participants [Participants]	12 100%

Adverse Events

Time Frame	Weekly during radiation therapy. After completion of therapy at 6-12 weeks , 6 months, and annually during follow-up. Patients are followed for 5 years or until death, whichever occurs first. Study was terminated before planned and participants were only followed for a median duration of 2 years.
Adverse Event Reporting Description	Toxicity is evaluated with physical exams; cardiology exams (Echocardiogram and Electrocardiogram); pulmonary function tests (Diffusing capacity of the lungs for carbon monoxide (DLCO), forced exhaled volume in 1 second (FEV 1) and FEV1 / FVC (forced vital capacity); and laboratory tests.
Arm/Group Title	Proton Radiation
Arm/Group Description	Proton Radiation, delivered daily (Monday-Friday) for two to five weeks.
All Cause Mortality
	Proton Radiation
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Proton Radiation
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Proton Radiation
	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)
Cardiac disorders
Cardiac disorders - Other, specify	1/11 (9.1%)	1
Palpitations	1/11 (9.1%)	1
Sinus bradycardia	1/11 (9.1%)	1
Ear and labyrinth disorders
Tinnitus	1/11 (9.1%)	1
Gastrointestinal disorders
Constipation	1/11 (9.1%)	1
Dysphagia	2/11 (18.2%)	2
Esophageal obstruction	1/11 (9.1%)	1
Esophagitis	2/11 (18.2%)	2
Gastroesophageal reflux disease	3/11 (27.3%)	3
Nausea	2/11 (18.2%)	2
Vomiting	1/11 (9.1%)	1
General disorders
Fatigue	6/11 (54.5%)	8
General disorders and administration site conditions - Other, specify	2/11 (18.2%)	2
Non-cardiac chest pain	1/11 (9.1%)	1
Pain	2/11 (18.2%)	2
Immune system disorders
Immune system disorders - Other, specify	1/11 (9.1%)	1
Infections and infestations
Upper respiratory infection	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Dermatitis radiation	9/11 (81.8%)	10
Investigations
Forced expiratory volume decreased	2/11 (18.2%)	2
Weight loss	1/11 (9.1%)	1
Metabolism and nutrition disorders
Anorexia	2/11 (18.2%)	2
Musculoskeletal and connective tissue disorders
Arthritis	1/11 (9.1%)	1
Osteoporosis	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/11 (9.1%)	1
Nervous system disorders
Headache	1/11 (9.1%)	1
Paresthesia	1/11 (9.1%)	1
Psychiatric disorders
Anxiety	3/11 (27.3%)	3
Insomnia	1/11 (9.1%)	1
Reproductive system and breast disorders
Irregular menstruation	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/11 (9.1%)	1
Dyspnea	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders - Other, specify	1/11 (9.1%)	1
Sore throat	1/11 (9.1%)	2
Skin and subcutaneous tissue disorders
Alopecia	3/11 (27.3%)	3
Pruritus	1/11 (9.1%)	1
Rash acneiform	1/11 (9.1%)	1
Skin hyperpigmentation	2/11 (18.2%)	2
Vascular disorders
Hot flashes	2/11 (18.2%)	2
Hypertension	1/11 (9.1%)	1
Thromboembolic event	1/11 (9.1%)	1

Limitations/Caveats

The study was terminated prematurely due to funding issues. Limited enrollment and shorter than planned follow-up prevented statistically significant evaluation of endpoints.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.