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| Name | Class |
|---|---|
| Fred Hutchinson Cancer Center | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Proton CSI Followed by Standard of Care (NSCLC & Breast) | Experimental | Proton CSI (30Gy [RBE] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice. |
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| Standard of Care | Experimental | 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. |
|
| Proton CSI Followed by Standard of Care (Other Solid Tumors) | Other | (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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Involved-field Photon Radiation Therapy | Radiation | Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions) |
|
| 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 |
| 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 |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Divya Yerramilli, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) | Basking Ridge | New Jersey | 07920 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40906462 | Derived | Yang JT, Yerramilli D, Pentsova E, Wolden S, Young RJ, Correa DD, Imber BS, Wijetunga NA, Goglia AG, Zhang Z, Zheng J, Baser R, Bernstein A, Kratochvil L, Xiao J, Hattangadi-Gluth J, Miller AM, Wilcox JA, Betof Warner A, Yu H, Kris MG, Seidman AD, Powell SN, Boire A. Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis: A Randomized Clinical Trial. JAMA Oncol. 2025 Nov 1;11(11):1293-1301. doi: 10.1001/jamaoncol.2025.3007. | |
| 35802849 |
| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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This is a randomized (2:1) phase II multicenter trial in patients with leptomeningeal metastases from NSCLC and breast cancer.
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| Proton Craniospinal Irradiation (CSI) | Radiation | Proton CSI (30Gy [RBE] in 10 fractions) |
|
| Neurocognitive Assessment | Other | 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. |
|
| MDASI-BT and MDASI-SP | Other | 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). |
|
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| Memorial Sloan Kettering Monmouth (Limitedl protocol activities) |
| Middletown |
| New Jersey |
| 07748 |
| United States |
| Memorial Sloan Kettering Bergen (Limited Protocol Activities) | Montvale | New Jersey | 07645 | United States |
| Memorial Sloan Kettering Commack (Limited Protocol Activities) | Commack | New York | 11725 | United States |
| Memorial Sloan Kettering Westchester (Limited Protocol Activities) | Harrison | New York | 10604 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Memorial Sloan Kettering Nassau (Limited Protocol Activities) | Uniondale | New York | 11553 | United States |
| Derived |
| Yang JT, Wijetunga NA, Pentsova E, Wolden S, Young RJ, Correa D, Zhang Z, Zheng J, Steckler A, Bucwinska W, Bernstein A, Betof Warner A, Yu H, Kris MG, Seidman AD, Wilcox JA, Malani R, Lin A, DeAngelis LM, Lee NY, Powell SN, Boire A. Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis. J Clin Oncol. 2022 Nov 20;40(33):3858-3867. doi: 10.1200/JCO.22.01148. Epub 2022 Jul 8. |
| ID | Term |
|---|---|
| D055756 | Meningeal Carcinomatosis |
| ID | Term |
|---|---|
| D008577 | Meningeal Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000073216 | Mental Status and Dementia Tests |
| ID | Term |
|---|---|
| D009483 | Neuropsychological Tests |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
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