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

NCT04343573 | Completed Phase 2 FDA Device

• 1 other identifier: 20-117
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Leptomeningeal Metastases

Keywords

Proton Craniospinal Irradiation (CSI); Involved-field Photon Radiation Therapy; 20-117

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• overall survival (OS) (Arm A and Arm B)

  2 years

Study Arms (3)

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.

Radiation: Proton Craniospinal Irradiation (CSI); Other: Neurocognitive Assessment; Other: MDASI-BT and MDASI-SP

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.

Radiation: Involved-field Photon Radiation Therapy; Other: Neurocognitive Assessment; Other: MDASI-BT and MDASI-SP

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.

Radiation: Proton Craniospinal Irradiation (CSI); Other: Neurocognitive Assessment; Other: MDASI-BT and MDASI-SP

Interventions

Involved-field Photon Radiation Therapy RADIATION

Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions)

Standard of Care

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).

Also known as: MD Anderson Symptom Inventory for brain tumors, MD Anderson Symptom Inventory for spine tumors

Proton CSI Followed by Standard of Care (NSCLC & Breast); Proton CSI Followed by Standard of Care (Other Solid Tumors); Standard of Care

Proton Craniospinal Irradiation (CSI) RADIATION

Proton CSI (30Gy \[RBE\] in 10 fractions)

Proton CSI Followed by Standard of Care (NSCLC & Breast); Proton CSI Followed by Standard of Care (Other Solid Tumors)

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.

Proton CSI Followed by Standard of Care (NSCLC & Breast); Proton CSI Followed by Standard of Care (Other Solid Tumors); Standard of Care

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Fred Hutchinson Cancer Center: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limitedl protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Publications (2)

• 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.

  PMID: 40906462 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.

  PMID: 35802849 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Mental Status and Dementia Tests

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Divya Yerramilli, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized (2:1) phase II multicenter trial in patients with leptomeningeal metastases from NSCLC and breast cancer.

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: April 13, 2020
• Study Start: April 10, 2020
• Primary Completion: February 25, 2026
• Study Completion: February 25, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)