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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 2

Conditions: Leptomeningeal Metastases

Treatments: Radiation: Proton Craniospinal Irradiation (CSI); Other: MDASI-BT and MDASI-SP; Radiation: Involved-field Photon Radiation Therapy; Other: Neurocognitive Assessment

Study type: Interventional

Funder types: Other

Identifiers

NCT04343573

20-117

Details and patient eligibility

About

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.

Enrollment: 102 patients

Sex: All

Ages: Under 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 3 patient groups

Proton CSI Followed by Standard of Care (NSCLC & Breast)

Experimental group

Description:

Proton CSI (30Gy \[RBE\] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.

Treatment:

Other: Neurocognitive Assessment

Other: MDASI-BT and MDASI-SP

Radiation: Proton Craniospinal Irradiation (CSI)

Standard of Care

Experimental group

Description:

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.

Treatment:

Other: Neurocognitive Assessment

Radiation: Involved-field Photon Radiation Therapy

Other: MDASI-BT and MDASI-SP

Proton CSI Followed by Standard of Care (Other Solid Tumors)

Other group

Description:

(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.

Treatment:

Other: Neurocognitive Assessment

Other: MDASI-BT and MDASI-SP

Radiation: Proton Craniospinal Irradiation (CSI)