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

Primary Purpose

Leptomeningeal Metastases

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Involved-field Photon Radiation Therapy

Proton Craniospinal Irradiation (CSI)

Neurocognitive Assessment

MDASI-BT and MDASI-SP

About this trial

This is an interventional treatment trial for Leptomeningeal Metastases focused on measuring Proton Craniospinal Irradiation (CSI), Involved-field Photon Radiation Therapy, 20-117

Eligibility Criteria

undefined - 99 Years (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Memorial Sloan Kettering Monmouth (Limitedl protocol activities)
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Memorial Sloan Kettering Commack (Limited Protocol Activities)
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

Arm Label

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

Standard of Care

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

Arm Description

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

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.

(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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

will be included in an analysis of overall survival, defined as time from randomization to death.

Full Information

NCT ID

NCT04343573

First Posted

April 10, 2020

Last Updated

May 11, 2023

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Fred Hutchinson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04343573

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 10, 2020 (Actual)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Fred Hutchinson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leptomeningeal Metastases

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

102 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Standard of Care

Arm Type

Experimental

Arm 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.

Arm Title

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

Arm Type

Other

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Involved-field Photon Radiation Therapy

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Proton Craniospinal Irradiation (CSI)

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Neurocognitive Assessment

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

MDASI-BT and MDASI-SP

Other Intervention Name(s)

MD Anderson Symptom Inventory for brain tumors, MD Anderson Symptom Inventory for spine tumors

Intervention Description

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).

Primary Outcome Measure Information:

Title

CNS progression free survival

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

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

Description

will be included in an analysis of overall survival, defined as time from randomization to death.

Time Frame

2 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Divya Yerramilli, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

City

Basking Ridge

State/Province

New Jersey

ZIP/Postal Code

07920

Country

United States

Facility Name

Memorial Sloan Kettering Monmouth (Limitedl protocol activities)

City

Middletown

State/Province

New Jersey

ZIP/Postal Code

07748

Country

United States

Facility Name

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

City

Montvale

State/Province

New Jersey

ZIP/Postal Code

07645

Country

United States

Facility Name

Memorial Sloan Kettering Commack (Limited Protocol Activities)

City

Commack

State/Province

New York

ZIP/Postal Code

11725

Country

United States

Facility Name

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

City

Harrison

State/Province

New York

ZIP/Postal Code

10604

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

City

Uniondale

State/Province

New York

ZIP/Postal Code

11553

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

Citations:

PubMed Identifier

35802849

Citation

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.

Results Reference

derived

Links:

URL

http://www.mskcc.org/mskcc/html/44.cfm

Description

Memorial Sloan Kettering Cancer Center

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

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