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

Phase 2

Active, not recruiting

• Conditions: Leptomeningeal Metastases
• Interventions: Radiation: Proton Craniospinal Irradiation (CSI); Radiation: Involved-field Photon Radiation Therapy; Other: Neurocognitive Assessment; Other: MDASI-BT and MDASI-SP

• Registration Number: NCT04343573
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-04-10
• Study First Submitted: 2020-04-10
• Study First Submitted QC: 2020-04-10
• Study First Posted: 2020-04-13
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-13
• Last Update Posted: 2024-05-14
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 102

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Proton CSI Followed by Standard of Care (Other Solid Tumors)	MDASI-BT and MDASI-SP	(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.
Proton CSI Followed by Standard of Care (NSCLC & Breast)	MDASI-BT and MDASI-SP	Proton CSI (30Gy \[RBE\] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.
Standard of Care	MDASI-BT and MDASI-SP	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 (NSCLC & Breast)	Proton Craniospinal Irradiation (CSI)	Proton CSI (30Gy \[RBE\] 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)	Proton Craniospinal Irradiation (CSI)	(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.
Proton CSI Followed by Standard of Care (Other Solid Tumors)	Neurocognitive Assessment	(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.
Proton CSI Followed by Standard of Care (NSCLC & Breast)	Neurocognitive Assessment	Proton CSI (30Gy \[RBE\] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.
Standard of Care	Involved-field Photon Radiation Therapy	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.
Standard of Care	Neurocognitive Assessment	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.

Primary Outcome Measures

Name	Time	Method
CNS progression free survival	2 years	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.

Secondary Outcome Measures

Name	Time	Method
overall survival (OS) (Arm A and Arm B)	2 years	will be included in an analysis of overall survival, defined as time from randomization to death.

Trial Locations

Locations (7)

Memorial Sloan Kettering Nassau (Limited Protocol Activities); 🇺🇸 Uniondale, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities); 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limitedl protocol activities); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities); 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Commack (Limited Protocol Activities); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities); 🇺🇸 Harrison, New York, United States