Neoplasms

All Conditions

Rare Diseases

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

At the initiation of the surgical phase maximal safe resection will be undertaken, and after 25 + 4 from surgery participants will start the concomitant phase and receive daily temozolomide (TMZ, 75mg/m2) and 20 fractions external beam radiation (EBRT). The EBRT treatment will be to the operative bed and any residual disease identified at the time of the imaging obtained for EBRT planning. The EBRT planning will utilize the GT implant dosimetry with the intent that the dose received from the GT will be accounted for during the EBRT treatment planning process. Twenty-eight days ±7 after the completion of concomitant TMZ and EBRT, participants will enter the adjuvant phase and will be treated with TMZ (150-200mg/m2) for 5 days at the start of every 28- day cycle, for 6 cycles.

Surgical tumor resection, GammaTile radiation therapy implantation, Stupp protocol (EBRT and Temozolamide)

Michael A. Garcia, MD, MS

Sita Patel, PhD, PharmD

John Wanebo, MD

Aida Lozada

Eric Chang, MD

Orin Bloch, MD

John David, MD

Adam W Nowlan, MD, MPH

Marissa Lowe

Mitesh Shah, MD

Tolga Tuncer, MD

Clark Chen, MD

Stuart Lee, MD

Mark Hoeprich, MD

Jennifer Thomas

Karen Fink, M.D., Ph.D.

In summary, standard of care postoperative chemoradiation for patients with newly diagnosed GBM does not routinely provide durable local control or prolonged overall survival. As discussed above it seems unlikely that patient outcomes will be significantly improved with radiation dose escalation given at the time of the EBRT boost. However, as most failures are local, improving LC could potentially improve the OS of patients. To do this, we propose a shift in the traditional radiation paradigm. This study will assess the feasibility and tolerability of adding GT radiation therapy as an upfront boost at the time of maximum safe resection, along with the backbone of the current standard of care approach, concomitant and adjuvant temozolomide +/- TTF, for patients with newly diagnosed GBM. GT, a novel brain brachytherapy device utilizing Cs-131 embedded in bioresorbable collagen tiles, offers a more sophisticated carrier and a shorter half-life radioisotope, Cs-131. Use of this device allows for radiation initiation at an earlier time point and a more rapid dose delivery and possibly more effective tumor control particularly for rapidly proliferating tumors such as GBM. Two prospective studies have demonstrated the safety and efficacy of re-irradiation with GT in patients with recurrent GBM. The overarching goal of this single-arm, open label phase 4 study is to determine the feasibility and tolerability of treating patients with GammaTile in combination with the Stupp Protocol and how to proceed with testing this treatment in a future, larger, randomized clinical study. The aims of the study are to demonstrate that the use of GammaTile at the time of surgery is well tolerated and does not delay the start of the Stupp protocol. Efficacy outcomes (e.g., LC, OS, PFS) will also be described.

This study seeks to explore if GT, given its unique radiobiological and physical characteristics, may permit safe dose escalation and intensification and thereby provide a benefit to newly diagnosed GBM patients in terms of OS and LC when incorporated into the framework of the Stupp protocol. In this study, GT is utilized as an upfront boost at the time of maximum safe resection and dosimetrically integrated into what is otherwise standard of care therapy.

Patients in this study will receive doses from two different forms of radiation treatment, initially from Cs-131 BT with GT and subsequently from fractionated EBRT. In order to ensure both patient safety and adequacy of treatment, we have chosen to stipulate and evaluate the coverage of the tumor volumes and OARs using the doses combined from both these treatments. The intention is that with this methodology the doses received by the target volumes and relevant OARs from the implanted Cs-131 will be accounted for during EBRT treatment planning. This dose combination, accomplished using radiobiological modeling, is frequently undertaken in breast, prostate, and gynecological malignancies. To provide oversight and planning feedback, the first three patients enrolled at each site will undergo review by the Clinical Oversight Committee (COC) at two points for each patient, once after the GT implant, and before starting EBRT treatment.

The intervention is the addition of GammaTile radiation therapy to the standard of care Stupp Protocol treatment of newly diagnosed GBM patients.

GammaTile and Stupp in Newly Diagnosed GBM

Pilot Study of Resection and GammaTile Followed by Concomitant External Beam Radiation Therapy (EBRT) and Temozolomide (TMZ) and Adjuvant in Newly Diagnosed Glioblastoma (GBM)

Complications can occur with any neurosurgical procedure and include but are not limited to problems with wound healing, cerebrospinal fluid leaks, infection, acute or delayed hemorrhage, seizures, and adhesion formation. EBRT complications can include but are not limited to nausea, vomiting, alopecia, skin toxicity, vertigo, problems with attention or concentration, worsening neurological symptoms, and radionecrosis of brain and non-brain tissues.

For this feasibility study, median overall survival, and overall survival at 12, 18 and 24 months will be analyzed in both the ITT and per protocol population.

Progression Free Survival (PFS) is defined as time from the date of surgery to date of progression, death, or last known follow-up (censored).

The Karnofsky Performance Status Scale is used to assess functional impairment. Score 0 to 100, with 100 being no impairment of performance

The Eastern Cooperative Oncology Group Performance Status scale is a simple, 5 point scale that can be used in daily practice measure tp measure functional status. Scores of 0-5 with 0 being fully active, and 10 being dead.

The immune system plays a major role in suppressing the development and growth of primary brain tumors. Therefore immune competence will also be measured by assessing absolute lymphocyte counts.

Systematic evaluation of the toxicity outcomes using this methodology is an exploratory objective of the study.

Assessment of the impact of therapy on immune competence.

Assessment of the incidence of radiation toxicity

Feasibility of using GammaTiles in patients who will also be treated with the Stupp Protocol.

Safety of treating patients treated with GammaTiles in addition to the Stupp protocol.

Secondary safety endpoint-assessment of safety in those patients who were treated per protocol

Spots Global Cancer Trial Database for surgical tumor resection, gammatile radiation therapy implantation, stupp protocol (ebrt and temozolamide)