A Phase II Trial of Limited Surgery and Proton Therapy for Craniopharyngioma or Observation After Radical Resection

A Phase II Trial of Limited Surgery and Proton Therapy for Craniopharyngioma and Observation for Craniopharyngioma After Radical Resection

The goal of this study is to determine the feasibility and safety of treating patients with a brain tumor known as craniopharyngioma with limited surgery and a 5mm clinical target volume margin in combination with proton therapy. Proton therapy will be indicated for patients with diagnosed craniopharyngioma who are not treated with radical surgery (gross-total resection). Irradiated patients will undergo a series of evaluations designed to evaluate the effects of proton therapy. Similar evaluations will be performed on patients treated with radical surgery. Proton therapy will include 30 treatment fractions administered 5 days per week. Weekly imaging will be a requirement to monitor for cyst expansion and target volume deformation.

Study Overview

• Status: Active, not recruiting
• Conditions: Craniopharyngioma
• Intervention / Treatment: Drug: ^1^1C-methionine; Procedure: Radical Surgery or Limited Surgery; Device: Proton Therapy; Drug: ^1^8F-fluorodeoxyglucose

Detailed Description

The primary objectives of this study :

To estimate the progression-free and overall survival distributions for children and young adults with craniopharyngioma treated with limited surgery and proton therapy using a 5mm clinical target volume margin while monitoring for excessive central nervous system necrosis.

The Secondary Objectives of this study:

• To estimate the cumulative incidence of cystic intervention and the event-free survival distribution for children and young adults with craniopharyngioma treated with limited surgery and proton therapy using a 5mm clinical target volume margin; and compare the distributions of progression-free, event-free and overall survival with the distributions for the St. Jude Children's Research Hospital cohort of 93 patients on which the design of this trial is based.
• To estimate the distributions of progression-free survival and overall survival for children and young adults with craniopharyngioma treated only with primary surgical resection and to compare these distributions with the distributions observed for patients treated with limited surgery and proton therapy.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32206
      • University of Florida Health Proton Therapy Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Craniopharyngioma diagnosed by histology, cytology or neuroimaging.
• Patients ages 0-21 years at the time of diagnosis.

Exclusion Criteria

• Prior history of fractionated radiation therapy.
• Prior treatment with intracystic P-32, intracystic bleomycin or radiosurgery.
• Pregnant females are excluded. Radiation has teratogenic or abortifacient effects.

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

Other: Craniopharyngioma Patients; Craniopharyngioma patients will have limited surgery and a 5mm clinical target volume margin in combination with proton therapy. Proton therapy will be indicated for patients with diagnosed craniopharyngioma who are not treated with radical surgery (gross-total resection). Patients who have had radical surgery or limited surgery prior to enrollment on this study and have no evidence of tumor will be observed for 5 years. Participants receive ^1^8F-fluorodeoxyglucose and ^1^1C-methionine will be given to aid in tumor visualization.

Drug: ^1^1C-methionine; This is a contrast media that will be given intravenously to aid in tumor visualization.; Other Names: Contrast Media; Procedure: Radical Surgery or Limited Surgery; Patients will be selected for radical surgery based on the neurosurgeon's assessment that a Gross-Total Resection may be achieved with acceptable post-operative morbidity. The goal of surgical intervention in this study should be to facilitate tumor control, keeping surgical morbidity to a minimum. Common indications for surgical intervention directed at the tumor will include establishing a tissue diagnosis, tumor control by radical resection, relieving tumor mass effect to reduce symptoms and decreasing the target volume for proton therapy by planned volume reduction surgery. These indications can be achieved through radical or limited surgery.; Device: Proton Therapy; Proton therapy will be started once a final treatment plan has been developed and approved. There is no time limit for the interval from enrollment to when proton therapy commences. The total prescribed dose will be 54CGE administered at 1.8CGE per fraction. The time course of administration will be one fraction per day, 5 days per week, for a period of 6 weeks. Radiation will be prescribed to the planning target volume which will include the tumor bed encompassed by an anatomically defined margin meant to include subclinical microscopic disease, and an additional geometric margin that is meant to account for the technical limitations associated with planning and administering daily fractionated treatment. Making radiation therapy safer through the use of proton therapy.; Other Names: Radiation; Drug: ^1^8F-fluorodeoxyglucose; This is a contrast media that will be given intravenously to aid in tumor visualization.; Other Names: Contrast Media; ^1^8F-FDG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the progression-free and overall survival distributions for children and young adults with craniopharyngioma treated with limited surgery and proton therapy	Reducing the clinical target volume margin to 5mm and using proton therapy, with the goal of reducing side effects from irradiation, will not increase the rate of tumor progression compared to photon therapy with a similar or larger clinical target volume margin.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the cumulative incidence of cystic intervention and the event-free survival distribution for children and young adults with craniopharyngioma treated with limited surgery and proton therapy	This will be improved by models based on clinical and treatment factors and longitudinal measures of CNS effects.	5 years
Estimate the distributions of progression-free survival and overall survival for children and young adults with craniopharyngioma treated only with primary surgical resection	This will be improved by models based on clinical and treatment factors and longitudinal measures of CNS effects	5 years

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Thomas E Merchant, DO, PhD, St. Jude Children's Research Hospital

Publications and helpful links

General Publications

• Wilson LJ, Pirlepesov F, Moskvin V, Li Z, Guo Y, Li Y, Merchant TE, Faught AM. Proton therapy delivery method affects dose-averaged linear energy transfer in patients. Phys Med Biol. 2021 Apr 1;66(7). doi: 10.1088/1361-6560/abe835. Erratum In: Phys Med Biol. 2021 Jul 05;66(14):

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2011
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimated): August 17, 2011

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Proton Therapy; Radical resection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Bone Diseases; Bone Neoplasms; Craniopharyngioma; Adamantinoma; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: RT2CR; NCI-2011-03707 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes