Glioblastoma Clinical Trial
Official title:
A Phase II/III Randomized, Open-Label Study of Toca 511, A Retroviral Replicating Vector, Combined With Toca FC With Temozolomide and Radiation Followed by Adjuvant Temozolomide and Toca FC Compared to Temozolomide and Radiation Followed by Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma
This phase II/III trial studies how well vocimagene amiretrorepvec (Toca 511) and extended release flucytosine (Toca FC) work when added to the usual treatment (temozolomide and radiation therapy) in treating patients with newly diagnosed glioblastoma. Toca 511 is a live virus that has been built to carry a gene into tumor cells. This gene carries instructions that cause the tumor cells to turn Toca FC, typically used to treat fungal infections, into a drug that may kill the tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving Toca 511 and Toca FC in addition to the usual treatment (temozolomide and radiation therapy) may help shrink or stabilize cancer or extend the life of patients with newly diagnosed glioblastoma.
PRIMARY OBJECTIVES:
I. To compare the progression-free survival (PFS) of patients with newly diagnosed
glioblastoma treated with Toca 511 at the time of tumor resection followed by Toca FC in
combination with standard of care (SOC) treatment to patients with newly diagnosed
glioblastoma treated with SOC after tumor resection. (Phase II) II. To compare the overall
survival (OS) from time of randomization of all patients with newly diagnosed glioblastoma
treated with Toca 511 at the time of tumor resection followed by Toca FC in combination with
SOC treatment to patients with newly diagnosed glioblastoma treated with SOC after tumor
resection. (Phase III)
SECONDARY OBJECTIVES:
I. To evaluate the safety of each arm as administered in this study. II. To compare the OS
between arms (only for phase II part of the study). III. To compare the PFS between arms
using Response Assessment in Neuro-Oncology (RANO) (only for phase III part of the study).
IV. To evaluate the objective response rate (ORR) in patients with measurable disease at the
post-surgical scan.
V. To evaluate the effect of IDH mutation status on survival outcomes between arms.
VI. To evaluate the PFS and OS by extent of resection. VII. To evaluate the effect of MGMT
methylation status on survival outcomes between arms.
EXPLORATORY OBJECTIVES:
I. To evaluate the duration of response (DoR) in patients with measurable disease at the
post-surgical scan using mRANO.
II. To evaluate the effect of corticosteroids administration on efficacy of Toca 511 and Toca
FC.
III. To optimize quality assurance methodologies and processes for radiotherapy and imaging.
IV. To determine if there is a tumor-microenvironment signature based on ribonucleic acid
(RNA) sequencing that is associated with a selective increase in benefit from the addition of
Toca 511 and Toca FC.
V. To compare regional genomic heterogeneity and molecular profiles, as measured by RNA
sequencing and methylation analyses between arms.
VI. To compare quality of life (QOL), as measured by the European Organization for Research
and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Brain
Cancer Module (BN20), between arms.
VII. To compare health utilities, as measured by the EuroQoL 5-Dimension 5-Level (EQ-5D-5L),
between arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Beginning on week 5 following standard of care surgery, patients undergo radiation
therapy over 30 fractions 5 days per week for up to 6 weeks, and receive temozolomide orally
(PO) once daily (QD) for up to 49 days. At the discretion of treating physician, patients may
also receive novoTTF-100A (Optune) device 0-7 weeks following radiation and temozolomide
treatment. One month following completion of radiation therapy, patients continue to receive
temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the
absence of disease progression or unacceptable toxicity.
ARM II: Patients receive vocimagene amiretrorepvec via intracranial injection during surgery
on day 1. Beginning on week 5 following surgery, patients receive extended release
flucytosine PO three times daily (TID) for 7 consecutive days every 7 weeks. Patients also
undergo radiation therapy and receive temozolomide as in arm I. After completion of radiation
therapy and at the discretion of the treating physician, patients may continue to receive
extended release flucytosine PO TID for 7 consecutive days every 8 weeks in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up until progression then, every 3
months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05664243 -
A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
Completed |
NCT02768389 -
Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma
|
Early Phase 1 | |
Recruiting |
NCT05635734 -
Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
Completed |
NCT03679754 -
Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102
|
Phase 1 | |
Completed |
NCT01250470 -
Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma
|
Phase 1 | |
Terminated |
NCT03927222 -
Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma
|
Phase 2 | |
Recruiting |
NCT03897491 -
PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT03587038 -
OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma
|
Phase 1 | |
Completed |
NCT01922076 -
Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
|
Phase 1 | |
Recruiting |
NCT04391062 -
Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT03661723 -
Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT02655601 -
Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001
|
Phase 2 | |
Completed |
NCT02206230 -
Trial of Hypofractionated Radiation Therapy for Glioblastoma
|
Phase 2 | |
Completed |
NCT03493932 -
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
|
Phase 1 | |
Terminated |
NCT02709889 -
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT06058988 -
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
|
Phase 2 | |
Completed |
NCT03018288 -
Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)
|
Phase 2 | |
Withdrawn |
NCT03980249 -
Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells
|
Early Phase 1 | |
Not yet recruiting |
NCT04552977 -
A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma
|
Phase 2 | |
Terminated |
NCT02905643 -
Discerning Pseudoprogression vs True Tumor Growth in GBMs
|