Proton Craniospinal Radiation Therapy vs. Partial Photon Radiation Therapy for Leptomeningeal Metastasis From Solid Tumors

Study Overview
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Brief Summary
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The investigators are doing this study to find out whether proton craniospinal radiation therapy (proton CSI) or partial photon radiation therapy is more effective at preventing leptomeningeal metastasis from worsening. The proton CSI targets the entire space containing the CSF, brain, and spinal fluid. The partial photon radiation therapy treats only areas where the patient is having symptoms, such as the entire brain or part of the spine. The investigators also want to find out if proton CSI improves the symptoms patients may be experiencing because of the leptomeningeal metastasis. In addition, the investigators will compare the side effects of proton CSI and partial photon therapy. Patients undergoing proton beam RT will receive their treatment at the New York Proton Center in New York, NY. As part of the New York Proton Consortium, MSK has contracted for its faculty to treat patients at the New York Proton Center. If it is unfeasible for patients to get treated at NYPC, patients will have the decision to get treated at ProCure in Summerset, NJ.

Official Title
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A Phase II Randomized Study Assessing the Efficacy of Proton Craniospinal Irradiation (CSI) vs Involved-field Photon Radiation Therapy for Leptomeningeal Metastases From Solid Tumor Malignancies

Conditions
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Leptomeningeal Metastases

Intervention / Treatment
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* Radiation: Involved-field Photon Radiation Therapy
* Radiation: Proton Craniospinal Irradiation (CSI)
* Other: Neurocognitive Assessment
* Other: MDASI-BT and MDASI-SP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with solid tumor malignancy with leptomeningeal metastases established radiographically and/or through CSF cytology Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases Patients of all ages KPS ≥ 60 for participants ≥ 16 years old, and Lansky ≥ 60 for participants < 16 years old For adult patient, the patient/ legally authorized representative is able to provide informed consent. For pediatric patient, a parent is able to provide informed consent. Adequate bone marrow function: Hemoglobin > 8g/dL Absolute neutrophil count >1,000/mm Platelet count > 100,000/mm Female subjects must either be of non-reproductive potential (i.e. pediatric patients, OR postmenopausal by history [≥ 60 years old, or with no menses for >1 year without an alternative medical cause], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test within 2 weeks prior to starting treatment. Patient at reproductive potential must agree to practice an effective contraceptive method. Exclusion Criteria: Patient with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy Patient with extensive systemic disease and without reasonable systemic treatment options Patient who is unable to undergo MRI brain and spine with gadolinium contrast Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances Pregnant or lactating women.

Ages Eligible for Study
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Maximum Age: 99 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized (2:1) phase II multicenter trial in patients with leptomeningeal metastases from NSCLC and breast cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton CSI Followed by Standard of Care (NSCLC & Breast)<br>Proton CSI (30Gy [RBE] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice. | Radiation: Proton Craniospinal Irradiation (CSI)<br>* Proton CSI (30Gy [RBE] in 10 fractions)<br>Other: Neurocognitive Assessment<br>* All patients at MSKCC will complete a neurocognitive test battery at study entry (prior to RT), and approximately 3, 6 and 12 months and post -RT. The neurocognitive tests consists of standardized, validated and reliable measures of attention, executive functions, and memory, for which age- and education-matched healthy control published data are available. Patients will also complete self-report mood and fatigue scales at each of the same time points. This testing will only be done at MSKCC. Non-English-speaking patients and pediatric patients are exempt from completing the neurocognitive assessments. Neurocognitive assessments will be performed in person at MSK-Manhattan; an option to perform follow up assessments via telehealth will be available only for patients who are not able to go to Manhattan for these visits.<br>Other: MDASI-BT and MDASI-SP<br>* Using MDASI-BT and MDASI-SP questionnaires before, weekly during, at 3 months (+/- 4 weeks), 6 months (+/- 4 weeks), 9 months (+/- 4 weeks), and 12 months (+/- 4 weeks) after group assignment, and at CNS disease progression. Only one set needs to be completed. Non-English-speaking patients and pediatric patients are exempt from completing the patient-reported outcomes unless translated PRO assessment forms are available. Questionnaires will be completed via mail, in-person, or online (MSK Engage).<br>* Other names: MD Anderson Symptom Inventory for spine tumors;|
| Experimental: Standard of Care<br>Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice. | Radiation: Involved-field Photon Radiation Therapy<br>* Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions)<br>Other: Neurocognitive Assessment<br>* All patients at MSKCC will complete a neurocognitive test battery at study entry (prior to RT), and approximately 3, 6 and 12 months and post -RT. The neurocognitive tests consists of standardized, validated and reliable measures of attention, executive functions, and memory, for which age- and education-matched healthy control published data are available. Patients will also complete self-report mood and fatigue scales at each of the same time points. This testing will only be done at MSKCC. Non-English-speaking patients and pediatric patients are exempt from completing the neurocognitive assessments. Neurocognitive assessments will be performed in person at MSK-Manhattan; an option to perform follow up assessments via telehealth will be available only for patients who are not able to go to Manhattan for these visits.<br>Other: MDASI-BT and MDASI-SP<br>* Using MDASI-BT and MDASI-SP questionnaires before, weekly during, at 3 months (+/- 4 weeks), 6 months (+/- 4 weeks), 9 months (+/- 4 weeks), and 12 months (+/- 4 weeks) after group assignment, and at CNS disease progression. Only one set needs to be completed. Non-English-speaking patients and pediatric patients are exempt from completing the patient-reported outcomes unless translated PRO assessment forms are available. Questionnaires will be completed via mail, in-person, or online (MSK Engage).<br>* Other names: MD Anderson Symptom Inventory for spine tumors;|
| Other: Proton CSI Followed by Standard of Care (Other Solid Tumors)<br>(Exploratory arm) Patients with solid tumor malignancies other than NSCLC or breast cancer will be enrolled to the exploratory proton CSI arm (Arm C) and will not undergo randomization. Proton CSI (30Gy [RBE] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice. | Radiation: Proton Craniospinal Irradiation (CSI)<br>* Proton CSI (30Gy [RBE] in 10 fractions)<br>Other: Neurocognitive Assessment<br>* All patients at MSKCC will complete a neurocognitive test battery at study entry (prior to RT), and approximately 3, 6 and 12 months and post -RT. The neurocognitive tests consists of standardized, validated and reliable measures of attention, executive functions, and memory, for which age- and education-matched healthy control published data are available. Patients will also complete self-report mood and fatigue scales at each of the same time points. This testing will only be done at MSKCC. Non-English-speaking patients and pediatric patients are exempt from completing the neurocognitive assessments. Neurocognitive assessments will be performed in person at MSK-Manhattan; an option to perform follow up assessments via telehealth will be available only for patients who are not able to go to Manhattan for these visits.<br>Other: MDASI-BT and MDASI-SP<br>* Using MDASI-BT and MDASI-SP questionnaires before, weekly during, at 3 months (+/- 4 weeks), 6 months (+/- 4 weeks), 9 months (+/- 4 weeks), and 12 months (+/- 4 weeks) after group assignment, and at CNS disease progression. Only one set needs to be completed. Non-English-speaking patients and pediatric patients are exempt from completing the patient-reported outcomes unless translated PRO assessment forms are available. Questionnaires will be completed via mail, in-person, or online (MSK Engage).<br>* Other names: MD Anderson Symptom Inventory for spine tumors;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CNS progression free survival | For Arm A and Arm B, which will be defined as the duration of time from the date of randomization to the time of progression of disease or death, whichever occurs first. The baseline imaging study will be the diagnostic imaging obtained at study entry. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) (Arm A and Arm B) | will be included in an analysis of overall survival, defined as time from randomization to death. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton Craniospinal Irradiation (CSI), Involved-field Photon Radiation Therapy, 20-117