Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study

Study Overview
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Brief Summary
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This phase II trial studies how well hypofractionated proton or photon radiation therapy works in treating patients with brain tumors. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells. A shorter duration of radiation treatment may avoid some of the delayed side effects of radiation while providing a more convenient treatment and reducing costs.

Detailed Description
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PRIMARY OBJECTIVE: I. To report 3 year local tumor control of moderately hypofractionated proton or photon therapy for benign intracranial tumors. SECONDARY OBJECTIVES: I. To demonstrate feasibility of moderate hypofractionation pencil beam scanning proton therapy for intracranial tumors. II. To report physician reported acute and late toxicity of moderate hypofractionation pencil beam scanning proton therapy for intracranial tumors according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. III. To report neurocognitive effects, health related quality of life, and patient reported toxicity for moderate hypofractionation pencil beam scanning proton therapy for intracranial tumors. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients with benign and radiographically diagnosed intracranial tumors undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 17 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity. COHORT II: Patients with pathologically confirmed World Health Organization (WHO) grade 2-3 meningiomas undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 20 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Official Title
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HiPPI: A Phase 2 Trial of Hypofractionated Pencil Beam Scanning Proton Therapy for Benign Intracranial Tumors

Conditions
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Schwannoma, Grade I Meningioma, Grade II Meningioma, Grade III Meningioma, Intracranial Neoplasm, Nerve Sheath Neoplasm, Pituitary Gland Adenoma

Intervention / Treatment
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* Radiation: Hypofractionated Radiation Therapy
* Radiation: Photon Beam Radiation Therapy
* Radiation: Proton Beam Radiation Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically or radiographically diagnosed benign intracranial or nerve sheath tumor, including meningiomas, pituitary adenomas, schwannomas. World Health Organization (WHO) grade 2-3 meningiomas are also allowed Recommended to receive proton or photon fractionated radiation therapy Signed informed consent Exclusion Criteria: Pregnant females are excluded. Female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy. FCBP must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. A female of childbearing potential (FCBP) is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (if age >= 55 years); if the female subject is < 55 years and she has been naturally postmenopausal for >= 1 year her reproductive status has to be verified by additional laboratory (lab) tests (< 20 estradiol OR estradiol < 40 with follicle stimulating hormone [FSH] > 40 in women not on estrogen replacement therapy) Prior radiation therapy that would overlap with current target volume Inability to undergo magnetic resonance imaging (MRI)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I (hypofractionated radiation therapy)<br>Patients with benign and radiographically diagnosed intracranial tumors undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 17 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity. | Radiation: Hypofractionated Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>* Other names: hypofractionation;Radiation: Photon Beam Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>Radiation: Proton Beam Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>* Other names: Radiation, Proton Beam;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Cohort II (hypofractionated radiation therapy)<br>Patients with pathologically confirmed World Health Organization (WHO) grade 2-3 meningiomas undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 20 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity. | Radiation: Hypofractionated Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>* Other names: hypofractionation;Radiation: Photon Beam Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>Radiation: Proton Beam Radiation Therapy<br>* Undergo hypofractionated proton or photon radiation therapy<br>* Other names: Radiation, Proton Beam;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local tumor control | Will assess local tumor control rate. Local tumor control is defined as freedom from progressive disease (PD). Will be calculated as the proportion of patients who did not experience PD within 3-year follow up with 95% binomial proportion confidence interval for the entire population and each cohort independently. The same calculation will be repeated for the entire study population and each cohort separately. Kaplan-Meier method will be used to estimate the local control rates for the entire population and each cohort independently. | Up to 3 years since enrollment | 
| Incidence of adverse events | Will be assessed and graded according to Common Terminology Criteria for Adverse Events version 5.0 | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive effects | Will be summarized by summary statistics. | Up to 3 years | 
| Health related quality of life | Will be summarized by summary statistics. | Up to 3 years |