Clinical trial NCT04343573: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Leptomeningeal Metastases
Keywords: Proton Craniospinal Irradiation (CSI)
Involved-field Photon Radiation Therapy
20-117
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Fred Hutchinson Cancer Center
First posted: 2020-04-13
Enrollment: 102
Sex: ALL
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized (2:1) phase II multicenter trial in patients with leptomeningeal metastases from NSCLC and breast cancer.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: CNS progression free survival
timeFrame: 2 years
Secondary outcomes:
measure: overall survival (OS) (Arm A and Arm B)
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limitedl protocol activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Divya Yerramilli, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.