Clinical trial NCT02792582: A Phase II Trial of Intensity-Modulated Proton Therapy for Incompletely Resected Craniopharyngioma and Observation for Craniopharyngioma After Radical Resection
Official title: A Phase II Trial of Intensity-Modulated Proton Therapy for Incompletely Resected Craniopharyngioma and Observation for Craniopharyngioma After Radical Resection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Craniopharyngioma
Keywords: Brain tumor
Pediatrics
Radiation therapy
Proton therapy
Surgery
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2016-06-07
Enrollment: 160
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Craniopharyngioma is a rare brain tumor that affects both children and adults. It arises in a region of the brain near the pituitary gland, visual pathways, and central blood vessels. Patients often present with headache, loss of vision or delayed growth. In some instances they may present with imbalance of water and salts in the body.

The treatment for craniopharyngioma may be radical surgery or a combination of surgery and radiation therapy. In some instances surgery is not required. If the tumor cannot be completely removed, radiation therapy may be required. In this study we will use the most advanced form of proton therapy which is called intensity-modulated proton therapy. This is a newer form of radiation therapy which has a number of advantages over older forms of proton therapy and conventional radiation therapy using x-rays.

The main goal of this study is to learn if proton therapy will effectively treat patients with craniopharyngioma brain tumors and reduce side effects compared to more traditional forms of radiation therapy.

Detailed description: This study will include participants who are diagnosed or presumed to have craniopharyngioma based on neuroimaging, intra-operative assessment, or the evaluation of cyst fluid or tissue after limited or radical surgery. When possible, participants will be enrolled on protocol prior to surgery.

PRIMARY OBJECTIVE:

* To estimate the distributions of progression-free and overall survival for children and young adults with craniopharyngioma treated with intensity-modulated proton therapy while monitoring for excessive central nervous system necrosis, clinically significant vasculopathy, and permanent neurological conditions or deficits.

SECONDARY OBJECTIVES:

* To estimate the cumulative incidence of cystic intervention and the event-free survival distribution for children and young adults with craniopharyngioma treated with intensity-modulated proton therapy; and to compare the distributions of progression-free, event-free and overall survival with the distributions for the St. Jude Children's Research Hospital (SJCRH) cohort of patients treated with photon therapy on which the design of this trial is based.
* To estimate the cumulative incidence of cystic intervention and the distributions of progression-free survival, overall survival and the event-free 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 proton therapy.

OTHER PRE-SPECIFIED OBJECTIVES:

* To explore potential associations of clinical and treatment factors with the incidence and severity of neurological, endocrine and cognitive deficits in children and young adults with craniopharyngioma treated with radical surgery or proton therapy. Descriptively compare findings for patients treated with proton therapy with the reported findings for the updated SJCRH cohort treated with photon therapy.
* Using specific measures of sleep quality, excessive daytime sleepiness, daytime activity, circadian rhythm, fatigue, symptom distresses, and quality of life, explore associations of sleep, fatigue and quality of life with other measures of central nervous system (CNS) effects, clinical and treatment factors in children and young adults with craniopharyngioma treated with radical surgery or proton therapy.
* To evaluate and explore differences in physical performance and movement in children and young adults with craniopharyngioma treated with radical surgery or proton therapy, using specific measures of overall physical performance, flexibility, balance, coordination, muscle strength and power, and cardiopulmonary fitness.
* Estimate and compare the response of residual tumor and the incidence and severity of structural, functional and vascular effects of normal brain in children and young adults with craniopharyngioma after treatment with radical surgery or proton therapy using specific methods of diffusion, contrast-enhancement, vascular and functional neuroimaging, and explore the association between these and other measures of CNS effects and clinical and treatment factors.
* Investigate the feasibility of using positron emission tomography (PET) as an in vivo dose and distal edge verification system for craniopharyngioma patients treated with proton therapy.
* Measure growth factor and cytokine responses in children and young adults with craniopharyngioma after treatment with radical surgery or proton therapy, and explore associations between these and other measures of CNS effects and clinical and treatment factors. Descriptively compare findings for patients treated with proton therapy with the reported findings for the updated SJCRH cohort treated with photon therapy.

Eligibility criteria: Inclusion Criteria:

* Craniopharyngioma diagnosed by histology, cytology or neuroimaging or intra-operative assessment
* Patients ages 0-21 years at the time of diagnosis

Exclusion Criteria:

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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 3 years after initiation of proton therapy
measure: Overall survival (OS)
timeFrame: 3 years after initiation of proton therapy
Secondary outcomes:
measure: Compare incidence of first cystic intervention with participants treated with conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: 3 years after initiation of proton therapy
measure: Compare event-free survival (EFS) with participants treated with conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: 3 years after initiation of proton therapy
measure: Compare survival distributions with participants treated with conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: 3 years after initiation of proton therapy
measure: Compare survival distributions between groups
timeFrame: 3 years after initiation of proton therapy
Other outcomes:
measure: Change in vision status compared between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Change in hearing status compared between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare number of neurological deficits to participants treated using conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare number of endocrine deficits to participants treated using conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare number of cognitive deficits to participants treated using conventional radiation therapy at St. Jude Children's Research Hospital
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare quality of life between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare physical performance and movement between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Incidence of vasculopathy between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Compare incidence of central nervous effects between groups
timeFrame: From baseline to 5 years following start of proton therapy
measure: Percentage of participants who were successfully evaluated with an in vivo dose and distal edge verification system
timeFrame: From baseline to 5 years following start of proton therapy
measure: Change in growth factor response
timeFrame: From baseline to 5 years following start of proton therapy
measure: Change in cytokine response
timeFrame: From baseline to 5 years following start of proton therapy
measure: Number and type of germline variations associated with craniopharyngioma
timeFrame: 5 years following start of proton therapy
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Thomas E. Merchant, DO, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.