Study of Proton Radiation to the Brain and Spinal Cord for Patients With Leptomeningeal Metastases

A Phase Ib Study With Dose Expansion Cohort of Proton Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumors

The purpose of this study is to find the safest and most effective dose for delivering proton beam to the space containing CSF, brain, and spinal cord, in treating leptomeningeal metastases. The researchers think that using proton beam radiation to treat the space containing CSF, brain, and spinal cord, instead of treating only the areas where the metastasized tumor cells are causing symptoms, would improve the treatment of this disease.

Study Overview

• Status: Completed
• Conditions: Leptomeningeal Metastases
• Intervention / Treatment: Radiation: Proton craniospinal irradiation (CSI)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Centre
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: >/= 60 years old and 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 with solid tumor malignancy with leptomeningeal metastases established radiographically and/or through CSF cytology.
• KPS ≥ 60.
• Age ≥ 10 years.
• For adult patient, the patient is able to provide informed consent. For pediatric patient, a parent is able to provide informed consent.
• Patient at reproductive potential must agree to practice an effective contraceptive method.

• Adequate bone marrow function:

  • Hemoglobin ≥ 8g/dL
  • Absolute neutrophil count ≥500/mm^3
  • Platelet count ≥ 100,000/mm^3

Exclusion Criteria:

• Patient with multiple, serious major neurologic deficits 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Proton Radiation; Patients will be enrolled to receive 30Gy (RBE) in 3Gy (RBE) or 25Gy (RBE) in 2.5Gy (RBE) fractions course of proton CSI. The first 3 patients will be enrolled at dose level 30Gy (RBE) in 3Gy(RBE) fractions. If 1 or fewer patients develop dose-limiting toxicity (DLT), 3 additional patients will be enrolled. If 1 or fewer of the 6 patients experiences a DLT, the trial will proceed to the dose expansion cohort at 30Gy (RBE) . In contrast, if 2 or more patients experience a treatment DLT, 3 patients will be enrolled at dose level 25Gy (RBE) in 2.5Gy(RBE) fractions. If 1 or fewer patients develop a DLT, an additional three patients will be enrolled. If 2 or more patients experience a DLT at 25Gy, the study will be stopped. If 1 or fewer patients develop a DLT in these 6 patients, the trial will proceed to the dose expansion cohort at 25Gy (RBE) and the 6 patients who were treated in Phase Ib will be included in full assessment of safety and efficacy.

Radiation: Proton craniospinal irradiation (CSI); Patients will be enrolled to receive 30Gy (RBE) in 3Gy (RBE) or 25Gy (RBE) in 2.5Gy (RBE) fractions course of proton CSI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with dose-limiting toxicity	will be assessed by physician-graded CTCEAv4	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Daniel Higginson, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2018
• Primary Completion (Actual): December 22, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: April 27, 2018
• First Submitted That Met QC Criteria: April 27, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Proton Radiation; craniospinal irradiation (CSI); 18-205
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Meningeal Neoplasms; Neoplasm Metastasis; Meningeal Carcinomatosis
• Other Study ID Numbers: 18-205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No