Adjuvant Stereotactic Fractionated Radiotherapy to the Resection Cavity in Recurrent Glioblastoma

NCT ID: NCT02715297

Last Updated: 2020-03-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2023-02-28

Brief Summary

This multi-center randomized controlled phase II trial will investigate the impact of stereotactic fractionated radiotherapy to the resection cavity of complete resected recurrent glioblastoma on progression free survival. As secondary endpoints, overall survival, safety and toxicity as well as early response criteria on MRI, quality of life and neurocognitive function will be assessed. Chemotherapy will not be part of the protocol, however, additional treatment will be possible upon investigators best choice.

Detailed Description

The treatment of recurrent glioblastoma is, beside of its abundance in clinical practice, still under discussion. Patients presenting with recurrent disease are therefore treated within individual concepts, largely based on small prospective trials, retrospective evaluations or case reports. Therefore, the treatment ranges from best supportive care over primary systemic treatments towards local therapies such as radiotherapy or surgical resection. Even if there might be a large selection bias, local therapies with or without concomitant or adjuvant chemotherapy seem to promise the largest prognostic benefit. Whether the combination of surgical resection and adjuvant radiotherapy improves survival, as it does within the primary situation, is unknown.

The result of surgical resection might have an impact as well. Several case reports, retrospective evaluations and prospective studies have also included patients with remaining gross tumor after maximum save resection. In these trials, radiotherapy was associated with improvements in progression free as well as overall survival. Therefore, the influence of neuroimaging on prognosis is currently evaluated within the GLIA-A trial. Furthermore, stereotactic radiotherapy with or without an experimental systemic therapy is currently investigated within another multicenter randomized trial (NOA-12).

Whether patients might benefit from a postoperative radiotherapy of the resection cavity after complete extirpation of all macroscopic tumor is key question of this protocol.

To answer this question, the considered standard of care after complete resection, namely observation with or without adjuvant systemic therapy, will be compared to a postoperative normofractionated stereotactic radiotherapy towards the resection cavity within an open label, randomized trial. The prescribed total dose will be 46 Gy in 2 Gy fractions of 36 Gy in 3 Gy fractions depending on the treatment volume.

Concerning safety, side effects will be monitored prospectively. Safety parameters will be compared between both arms of the study. Furthermore, measures for quality of life, neurocognitive function as well as neuroimaging features will be evaluated prospectively.

Conditions

Glioblastoma

Study Design

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

Study Groups

Arm A: SRT to the resection cavity

Postoperative stereotactic fractionated radiotherapy (SRT) to the resection cavity to a Total Dose of 46 Gy, 2 Gy single dose, or 36 Gy in 3 Gy single dose 5 fractions/week, depending on the volume and location of the treatment region.

Group Type: EXPERIMENTAL

SRT to the resection cavity

Intervention Type: RADIATION

46 Gy total dose will be delivered in 2 Gy per fraction, or 36 Gy delivered in 3 Gy per fraction, 5 fractions within 1 week. Doses will have to cover 95% of the PTV with the prescribed dose. The clinical target volume (CTV) will be defined as the resection cavity of the recurrent glioblastoma plus a margin of 5mm. A CTV to PTV margin of 1 to 3mm will be added according to technique used for immobilisation.

Arm B: Observation

Observation without adjuvant radiotherapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

SRT to the resection cavity

46 Gy total dose will be delivered in 2 Gy per fraction, or 36 Gy delivered in 3 Gy per fraction, 5 fractions within 1 week. Doses will have to cover 95% of the PTV with the prescribed dose. The clinical target volume (CTV) will be defined as the resection cavity of the recurrent glioblastoma plus a margin of 5mm. A CTV to PTV margin of 1 to 3mm will be added according to technique used for immobilisation.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Unifocal, supratentorial recurrent glioblastoma
• Prior course of standard treatment
• Complete resection of all contrast enhancing areas
• age ≥ 18 years of age
• Karnofsky Performance Score 60% or higher
• For women with childbearing potential, (and men) adequate contraception.
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria

• Multifocal glioblastoma of gliomatosis cerebri
• Time interval of less than 6 months after primary radiotherapy
• Previous re-irradiation or prior radiosurgery of prior treatment with interstitial radioactive seeds
• refusal of the patients to take part in the study
• Patients who have not yet recovered from acute toxicities of prior therapies
• Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
• Pregnant or lactating women
• Participation in another clinical study or observation period of competing trials, respectively.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helmholtz Zentrum München

INDUSTRY

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie E. Combs, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Klinik für RadioOnkologie und Strahlentherapie

Locations

Dept. Radiation Oncology

Munich, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Stephanie E. Combs, Prof. Dr.

Role: CONTACT

direktion.radonk@mri.tum.de

0049 89-41404501

Christoph Straube, Dr.

Role: CONTACT

christoph.straube@mri.tum.de

0049 89-41409411

Facility Contacts

Stephanie E. Combs, Prof. Dr.

Role: primary

direktion.radonk@mri.tum.de

089 4140 4501

Christoph Straube, Dr.

Role: backup

References

Straube C, Scherb H, Gempt J, Kirschke J, Zimmer C, Schmidt-Graf F, Meyer B, Combs SE. Adjuvant stereotactic fractionated radiotherapy to the resection cavity in recurrent glioblastoma - the GlioCave study (NOA 17 - ARO 2016/3 - DKTK ROG trial). BMC Cancer. 2018 Jan 3;18(1):15. doi: 10.1186/s12885-017-3928-7.

Reference Type: DERIVED

PMID: 29298660 (View on PubMed)

Other Identifiers

RadOnc MRI TUM - 1

Identifier Type: -

Identifier Source: org_study_id