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

Leptomeningeal Metastases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04343573
• Other study ID #: 20-117
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 10, 2020
• Est. completion date: April 2025

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leptomeningeal Metastases
• Meningeal Carcinomatosis
• Neoplasm Metastasis

Intervention

Radiation:
• Involved-field Photon Radiation Therapy
Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions)
• Proton Craniospinal Irradiation (CSI)
Proton CSI (30Gy [RBE] in 10 fractions)

Other:
• Neurocognitive Assessment
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
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).

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	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	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 Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Fred Hutchinson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

•   Memorial Sloan Kettering Cancer Center