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A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas

Primary Purpose

Meningioma, Brain Tumor

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intensity Modulated Proton Therapy (IMPT)
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Meningioma focused on measuring Tumor lining the brain, Meningioma, Brain Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must have either:

    • histologically confirmed atypical meningioma, WHO grade II, Simpson grade 4-5 that has been either subtotally resected or biopsied.

OR

  • histologically confirmed malignant/anaplastic meningioma, WHO grade III with any prior surgery.

In the case of recurrent radiographically gross disease, pathologic diagnosis may be from time of original biopsy and/or surgery. Pathology should be reviewed and confirmed at the Participating Institution.

Patients may or may not have neurofibromatosis type 1 or 2.

  • Age 18 years or older.
  • ECOG performance status ≤ 2 (Karnofsky Performance Status ≥ 60, see Appendix A)
  • The effects of proton radiation therapy on the developing human fetus are known to be teratogenic. For this reason, women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of proton therapy.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants may not be receiving any other investigational agents.
  • Participants may not have received prior cranial irradiation.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or lactating women are excluded from this study because radiation is known to have teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation therapy, breastfeeding should be discontinued if the mother is treated with radiation therapy.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

Sites / Locations

  • Massachusetts General HospitalRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Grade II (Atypical) Meningiomas, STR

Grade III (Malignant) Meningiomas, GTR

Grade III (Malignant) Meningiomas, STR

Arm Description

Patient will be treated at the starting dose of Intensity Modulated Proton Therapy (IMPT) which is pre-determined.

Patient will be treated at a pre determined dose of Intensity Modulated Proton Therapy (IMPT) for the specific cohort.

Patient will be treated at a pre determined dose of Intensity Modulated Proton Therapy (IMPT) for the specific cohort.

Outcomes

Primary Outcome Measures

Assess Safety and Utility of Increased Dose IMPT: Dose-limiting toxicity (DLT) using NCI CTC 4.0
Establish a safe increased-dose of post-operative IMPT with SIB in treating each of three meningioma cohorts: grade II (atypical) with subtotal resection, grade III (malignant) with gross total resection and grade III (malignant) with subtotal resection. Dose-limiting toxicity (DLT) using NCI CTC 4.0 will be assessed from the start of protocol treatment. The dose-seeking plan for each meningioma cohort will follow a modified 3+3 design with the starting and reduced doses for CTV and GTV.

Secondary Outcome Measures

The Absence of Progressive or Recurrent Disease
The duration of local tumor control will be measured from the start date of protocol treatment until the date of progressive or recurrent disease or censored at the date of last follow-up for patients still alive with stable disease. The rate of local failure will be estimated separately for each stratum based on the cumulative incidence, with death as a competing risk in the absence of progressive or recurrent disease.
Overall Survival
• Overall survival (OS) will be measured from the start date of protocol treatment until the date of death due to any cause or censored at the date of last follow-up for patients still alive. The rate of OS will be estimated separately for each stratum using the Kaplan-Meier method.
Calculate Linear Energy Transfer Using Computer Simulations Based on the Treatment Plan
• Linear energy transfer (LET) will be plotted against radiographic changes to assess the pattern of their correlation. Graphical methods and descriptive statistics will be used to determine if the relationship may be characterized by a formal model, possibly after data transformation. All strata will be pooled for the analyses of LET and the other physics endpoints, as they are functions of only the radiation physics, not histology or surgery.

Full Information

First Posted
January 13, 2016
Last Updated
August 17, 2020
Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02693990
Brief Title
A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas
Official Title
A Phase I/II Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Recruiting
Study Start Date
February 2016 (undefined)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This research study is studying radiation therapy as a possible treatment for meningioma or tumor on the lining of the brain. The study drug or intervention involved in this research study is Intensity Modulated Proton Therapy (IMPT)
Detailed Description
This is a Phase I/II clinical trial. Researchers are trying to find out if using increased-dose intensity modulated proton therapy (IMPT) for treatment of Meningiomas will be more effective than the current treatment. The intensity modulated part of IMPT allows for even better concentration of the radiation dose to the desired target and less dose to the surrounding normal tissues than even traditional passive scattering proton therapy can do. Proton beams can be regulated to stop within or shortly beyond treatment targets. Therefore there is little exposure of the normal tissue to radiation. The FDA (the U.S. Food and Drug Administration) has not approved IMPT as a treatment for any disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningioma, Brain Tumor
Keywords
Tumor lining the brain, Meningioma, Brain Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Grade II (Atypical) Meningiomas, STR
Arm Type
Experimental
Arm Description
Patient will be treated at the starting dose of Intensity Modulated Proton Therapy (IMPT) which is pre-determined.
Arm Title
Grade III (Malignant) Meningiomas, GTR
Arm Type
Experimental
Arm Description
Patient will be treated at a pre determined dose of Intensity Modulated Proton Therapy (IMPT) for the specific cohort.
Arm Title
Grade III (Malignant) Meningiomas, STR
Arm Type
Experimental
Arm Description
Patient will be treated at a pre determined dose of Intensity Modulated Proton Therapy (IMPT) for the specific cohort.
Intervention Type
Radiation
Intervention Name(s)
Intensity Modulated Proton Therapy (IMPT)
Intervention Description
Radiation Therapy - Intensity Modulated Proton Therapy (IMPT)
Primary Outcome Measure Information:
Title
Assess Safety and Utility of Increased Dose IMPT: Dose-limiting toxicity (DLT) using NCI CTC 4.0
Description
Establish a safe increased-dose of post-operative IMPT with SIB in treating each of three meningioma cohorts: grade II (atypical) with subtotal resection, grade III (malignant) with gross total resection and grade III (malignant) with subtotal resection. Dose-limiting toxicity (DLT) using NCI CTC 4.0 will be assessed from the start of protocol treatment. The dose-seeking plan for each meningioma cohort will follow a modified 3+3 design with the starting and reduced doses for CTV and GTV.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The Absence of Progressive or Recurrent Disease
Description
The duration of local tumor control will be measured from the start date of protocol treatment until the date of progressive or recurrent disease or censored at the date of last follow-up for patients still alive with stable disease. The rate of local failure will be estimated separately for each stratum based on the cumulative incidence, with death as a competing risk in the absence of progressive or recurrent disease.
Time Frame
5 years
Title
Overall Survival
Description
• Overall survival (OS) will be measured from the start date of protocol treatment until the date of death due to any cause or censored at the date of last follow-up for patients still alive. The rate of OS will be estimated separately for each stratum using the Kaplan-Meier method.
Time Frame
2 years
Title
Calculate Linear Energy Transfer Using Computer Simulations Based on the Treatment Plan
Description
• Linear energy transfer (LET) will be plotted against radiographic changes to assess the pattern of their correlation. Graphical methods and descriptive statistics will be used to determine if the relationship may be characterized by a formal model, possibly after data transformation. All strata will be pooled for the analyses of LET and the other physics endpoints, as they are functions of only the radiation physics, not histology or surgery.
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
In Vivo Range of the Delivered Proton Pencil-Beams
Description
For a small subset of the treatment fields delivered at MGH, a prompt gamma-ray spectroscopy system will be used to measure gamma-rays that are naturally emitted from proton reactions with the patient. Based on these measurements, the investigators will calculate the position in the patient of the end-of-range of the individual proton pencil-beams. The reproducibility and statistical precision of the calculated end-of-range positions will be reported.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have either: histologically confirmed atypical meningioma, WHO grade II, Simpson grade 4-5 that has been either subtotally resected or biopsied. OR histologically confirmed malignant/anaplastic meningioma, WHO grade III with any prior surgery. In the case of recurrent radiographically gross disease, pathologic diagnosis may be from time of original biopsy and/or surgery. Pathology should be reviewed and confirmed at the Participating Institution. Patients may or may not have neurofibromatosis type 1 or 2. Age 18 years or older. ECOG performance status ≤ 2 (Karnofsky Performance Status ≥ 60, see Appendix A) The effects of proton radiation therapy on the developing human fetus are known to be teratogenic. For this reason, women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of proton therapy. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants may not be receiving any other investigational agents. Participants may not have received prior cranial irradiation. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant or lactating women are excluded from this study because radiation is known to have teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation therapy, breastfeeding should be discontinued if the mother is treated with radiation therapy. Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Helen A Shih, MD
Phone
617-724-9627
Email
hshih@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tarin Grillo
Phone
617-724-3661
Email
tgrillo@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen A Shih, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helen A Shih, MD
Phone
617-724-9627
Email
hshih@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Helen A Shih, MD
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan McGovern, MD, PhD
Phone
713-563-2336
Email
slmcgove@mdanderson.org

12. IPD Sharing Statement

Learn more about this trial

A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas

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