Clinical trial NCT02394665
Conditions: Glioblastoma
Keywords: Glioblastoma Gliosarcoma GBM
Sponsor: University of Miami
Start date: 2015-03-01; Completion date: 2016-09-01
Enrollment: 1 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In summary, the overall prognosis of glioblastoma (GBM) patients remains poor. Although clinical gains have been achieved in the past, these have been modest, with a majority of patients succumbing to local disease progression within 2 years. New strategies for treatment need to be identified which enhance local control above the current treatment regimen in order to achieve further clinical gains in this disease. Favorable early experience with magnetic resonance spectroscopy imaging (MRSI) demonstrates that metabolic imaging can identify active tumor beyond standard MRI as well as high risk regions at risk for local failure. There is also clinical evidence that limited field dose escalation with either simultaneous integrated boost (SIB) or stereotactic radiosurgery (SRS) is feasible and safe. Coupling these findings provide the rationale for this proposed Phase II trial designed to define efficacy and toxicity of the novel treatment approach of whole brain volumetric 3D MRSI guided dose-escalated radiation therapy (RT) in newly diagnosed GBM patients.

Detailed description:
This phase II study will investigate efficacy and safety of volumetric 3D MRSI-directed treatment for newly diagnosed GBM patients. This study will enroll 48 patients in order to obtain at least 40 patients receiving RT and temozolomide. Depending on the size and number of HTVs, a patient will receive either simultaneous integrated boost (SIB) with IMRT (Group 1) or SRS boost followed by IMRT 1 week later (Group 2). Duration of enrollment will be 2 years and minimum follow-up will be 2 years.

The duration of treatment and follow-up will occur as follows:

* Six weeks of RT with concurrent Temozolomide treatment;
* 3D MRSI at week 3 and at the end of RT;
* 28 day break;
* Adjuvant treatment with Temozolomide administered daily on days 1-5 of each cycle, for up to 12 cycles (one cycle = 28 days) which will include standard gadolinium enhanced MRI and 3D MRSI prior to cycle 1, 5, 9, and post cycle 12 of adjuvant Temozolomide;
* Active follow-up at least every three months for one year after the end of adjuvant Temozolomide treatment;
* After one year follow-up for survival will occur every three months for one year.

Arms: arm 1: * Simultaneous Integrated Boost (SIB) plus Fractionated Intensity Modulated Radiation therapy (IMRT), with concurrent Temozolomide therapy for 6 weeks;
* 3D MRSI during week 3, end of RT and other protocol-defined time points during adjuvant Temozolomide therapy;
* Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire administered at protocol-defined time points;
* Adjuvant Temozolomide Therapy for up to 12 cycles. arm 2: For patients with High-Risk Tumor Volumes (HTV) \<= 4cm; or multiple HTVs \<= 3 cm:

* Stereotactic Radiosurgery Boost (SRS Boost) followed one week later by Fractionated Intensity Modulated Radiation therapy (IMRT), and concurrent Temozolomide therapy for 6 weeks;
* 3D MRSI during week 3, end of RT and other protocol-defined time points during adjuvant Temozolomide therapy;
* Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire administered at protocol-defined time points;
* Adjuvant Temozolomide Therapy for up to 12 cycles.
Interventions: intervention 1: Intensity Modulated Radiation Therapy intervention 2: Temozolomide intervention 3: Functional Assessment of Cancer Therapy-Brain (FACT-Br) intervention 4: Stereotactic Radiosurgery Boost intervention 5: Simultaneous Integrated Boost intervention 6: 3D MRSI
Intervention descriptions: intervention 1: IMRT treatment will consist of 60 Gy in 30 fractions to PTV 60 intervention 2: Concurrently during radiation therapy. Adjuvant therapy administered daily on days 1 - 5 for 12 cycles. One cycle = 28 days:

* Concurrent during Radiation Therapy: 75 mg/m\^2 orally for 6 weeks;
* Post-radiation, adjuvant therapy: 150 mg/m\^2 - 200 mg/m\^2 orally daily on days 1 - 5 of each cycle. intervention 3: FACT-Br Quality of Life (QOL) questionnaire to be completed by study patients as protocol specific timepoints intervention 4: Patients will undergo SRS boost in a single fraction dose prior to IMRT treatment:

HTV Maximum dimension vs. Prescribed Dose to HTV: ≤ 20 mm = 21 Gy; 21 mm - 30 mm = 18 Gy; 31 mm - 40 mm = 15 Gy. intervention 5: Treatment shall consist of 60 Gy in 30 fractions to planning target volume (PTV) 60 and 75 Gy in 30 fractions to PTV 75. intervention 6: Three Dimensional Magnetic Resonance Spectroscopy Imaging (MRSI) during pre-treatment, week 3 during radiation therapy, end of radiation therapy; will include standard gadolinium enhanced MRI prior to cycle 1, 5, 9, and post cycle 12 of adjuvant temozolomide therapy, per protocol.

Protocol documents: