Intensity Modulated PrOton Therapy in Pediatric BRain Tumors (IMPORT)

NCT ID: NCT07338526

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-07
• Study Completion Date: 2035-07-07

Brief Summary

Children diagnosed with benign or low-grade brain tumors often require radiation therapy to control their disease. While radiation can be effective, traditional techniques using X-rays (photon-based radiotherapy) expose healthy brain tissue to radiation, potentially leading to long-term side effects like memory loss, learning difficulties, hormone imbalances, hearing problems, and a higher risk of secondary cancers. This study, called the IMPORT Trial, aims to compare two types of radiation therapy-Intensity-Modulated Proton Therapy (IMPT) and Intensity-Modulated Radiation Therapy (IMRT)-to determine which is safer and more effective for children. IMPT, a newer technique, uses protons instead of X-rays to deliver radiation, reducing exposure to healthy brain tissue. Researchers believe this could help minimize long-term damage while maintaining effective tumor control.

What is the goal of the study?

The primary goal is to see if IMPT leads to better survival with fewer side effects compared to IMRT. The study will track how well children function over five years, looking at:

• Cognitive abilities (memory, attention, learning)
• Hormonal balance (pituitary gland function)
• Hearing ability
• Overall survival without significant decline in quality of life

How will the study work?

• Who can join? Children aged 6 to 16 years diagnosed with certain types of benign or low-grade brain tumors.
• How are patients treated? Patients will be randomly assigned to receive either IMRT or IMPT.
• What is analysed? Doctors will track survival, tumor control, cognitive function, endocrine health, and quality of life over time.
• How long will it take? The study will last 10 years (5 years to enroll patients, 5 years to follow up).

Proton therapy is more expensive and not widely available, so strong scientific evidence is needed to justify its use in routine treatment. If IMPT significantly improves quality of life and survival, it could become the preferred treatment, shaping future policies and making proton therapy more accessible for children who need it.

Detailed Description

Benign and low-grade primary brain tumors constitute a substantial proportion of pediatric central nervous system tumors and are associated with excellent long-term survival when managed with multimodality therapy. Despite favorable tumor control rates, survivors are at significant risk of treatment-related late effects, particularly following radiation therapy, which can adversely impact neurocognitive function, endocrine health, auditory function, and overall quality of life. Given the prolonged life expectancy of this population, minimizing radiation-induced toxicity while maintaining effective disease control is a major therapeutic priority.

Radiation therapy remains an essential curative modality for children with unresectable, residual, progressive, or recurrent benign and low-grade brain tumors. Advances in high-precision photon-based techniques such as intensity-modulated radiation therapy (IMRT) have improved dose conformality; however, photon therapy continues to expose large volumes of normal brain tissue to low and intermediate radiation doses. This exposure may lead to white matter injury, neuroinflammation, microvascular damage, and subsequent neurocognitive, endocrine, and auditory dysfunction, particularly in younger patients with developing brains.

Proton beam therapy offers a potential dosimetric advantage over photon therapy due to its physical depth-dose characteristics, allowing reduced integral dose to surrounding normal tissues. Intensity-modulated proton therapy (IMPT), delivered using pencil beam scanning, enables highly conformal dose distributions with improved sparing of organs at risk and may allow for reduction in treatment margins through enhanced image guidance and dose painting capabilities. These properties suggest a potential for meaningful reduction in late radiation-related toxicity in pediatric patients, while preserving tumor control.

While dosimetric and retrospective clinical data suggest advantages of proton therapy in reducing radiation exposure to critical neural structures, robust prospective randomized evidence demonstrating clinically meaningful benefits remains limited. Furthermore, the higher cost and limited availability of proton therapy necessitate careful evaluation of its value relative to advanced photon techniques, particularly in resource-constrained healthcare systems. Generating high-level evidence to guide patient selection and policy decisions is therefore essential.

The IMPORT trial is a prospective, randomized, open-label, phase III superiority study designed to compare IMPT with IMRT in children with benign and low-grade primary brain tumors treated with curative intent radiotherapy. The trial focuses on outcomes that are particularly relevant to long-term pediatric survivorship, including neurocognitive function, endocrine and auditory toxicity, and quality of life, while ensuring comparable tumor control.

The study introduces the concept of Qualified Overall Survival (qOS) as a composite primary endpoint that integrates survival, disease control, and clinically significant treatment-related morbidity. This composite endpoint is intended to capture outcomes that reflect both oncologic efficacy and functional preservation, thereby providing a patient-centered assessment of treatment benefit.

Participants will be randomized to receive either IMPT or IMRT, with radiation dose, fractionation, and target volumes determined by tumor type, location, and standard clinical practice. Tumor response and disease progression will be assessed using contemporary imaging-based criteria, while functional outcomes will be evaluated using standardized neurocognitive testing, endocrine assessments, audiological evaluations, and patient-reported quality-of-life instruments.

By directly comparing IMPT and IMRT in a randomized setting, the IMPORT trial aims to determine whether the dosimetric advantages of proton therapy translate into superior long-term functional outcomes and improved qualified survival, thereby informing evidence-based clinical decision-making and health policy for pediatric brain tumor management.

Conditions

Brain Tumor Benign; Brain Tumor, Pediatric

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Arm

Patients in the standard arm will undergo focal cranial radiotherapy using photons (X-rays) with Image Guided Intensity Modulated Radiotherapy(IG-IMRT) using Volumetric Modulated Arc Therapy(VMAT).

Group Type: OTHER

Photon-based intensity-modulated radiation therapy (IMRT).

Intervention Type: RADIATION

Patients in the control arm will receive focal cranial radiotherapy using photon-based IG-IMRT delivered with VMAT. Dose, fractionation, and target volumes will follow standard institutional protocols based on tumor type and molecular features. Planning CT and MRI fusion will guide contouring of GTV, CTV, PTV, and organs at risk. Treatment plans will be generated in the Treatment Planning System and reviewed in multidisciplinary meetings. Radiotherapy will be delivered on IGRT-equipped linear accelerators, with weekly assessments for acute toxicities and routine follow-up imaging as per standard care.

Experimental Arm

The patients in the experimental arm will undergo focal radiotherapy to an equivalent dose using protons with pencil beam scanning- IMPT or volumetric modulated proton arc therapy.

Group Type: EXPERIMENTAL

Intensity-modulated proton therapy (IMPT)

Intervention Type: RADIATION

Patients in the experimental arm will receive focal cranial radiotherapy using proton therapy delivered with IMPT or proton arc techniques. Dose prescriptions and volumes will match institutional standards independent of study allocation. Planning will include CT and MRI fusion, with target and OAR delineation identical to the control arm. Proton plans will use robust optimization and undergo multidisciplinary review. Treatment will be delivered with image guidance, with weekly toxicity monitoring and standard clinical and imaging follow-up.

Interventions

Intensity-modulated proton therapy (IMPT)

Patients in the experimental arm will receive focal cranial radiotherapy using proton therapy delivered with IMPT or proton arc techniques. Dose prescriptions and volumes will match institutional standards independent of study allocation. Planning will include CT and MRI fusion, with target and OAR delineation identical to the control arm. Proton plans will use robust optimization and undergo multidisciplinary review. Treatment will be delivered with image guidance, with weekly toxicity monitoring and standard clinical and imaging follow-up.

Intervention Type: RADIATION

Photon-based intensity-modulated radiation therapy (IMRT).

Patients in the control arm will receive focal cranial radiotherapy using photon-based IG-IMRT delivered with VMAT. Dose, fractionation, and target volumes will follow standard institutional protocols based on tumor type and molecular features. Planning CT and MRI fusion will guide contouring of GTV, CTV, PTV, and organs at risk. Treatment plans will be generated in the Treatment Planning System and reviewed in multidisciplinary meetings. Radiotherapy will be delivered on IGRT-equipped linear accelerators, with weekly assessments for acute toxicities and routine follow-up imaging as per standard care.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Age at irradiation: 6 to 16 years
• Karnofsky/ Lansky Play Performance Status ≥ 60
• Diagnosis (histopathological/ radiological) of primary brain tumor with an expected survival of >5 years (e.g., circumscribed gliomas, low grade gliomas, low-grade glial/ glioneuronal tumors, meningioma, pituitary tumors, schwannoma, craniopharyngioma, ependymoma)
• Planned for focal cranial radiotherapy
• Informed consent taken

Exclusion Criteria

• Re-irradiation
• Palliative radiotherapy
• Multifocal or multicentric disease
• Planned for whole brain irradiation or craniospinal irradiation
• Planned for hypo-fractionated or stereotactic radiotherapy

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tata Memorial Hospital

Mumbai, Maharashtra, India

Site Status: RECRUITING

Countries

India

Central Contacts

Abhishek Chatterjee, MD

Role: CONTACT

chatterji08@gmail.com

2224177000 ext. 6015

Facility Contacts

Abhishek Chatterjee, MD

Role: primary

chatterji08@gmail.com

2224177000 ext. 6015

Other Identifiers

4785

Identifier Type: -

Identifier Source: org_study_id