Clinical Trials Directory

Trials / Withdrawn

WithdrawnNCT04105374

Testing the Addition of an Anti-cancer Viral Gene Therapy, Toca 511/Toca FC, to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed Glioblastoma

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

Status
Withdrawn
Phase
Phase 2 / Phase 3
Study type
Interventional
Enrollment
0 (actual)
Sponsor
NRG Oncology · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

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.

Detailed description

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.

Conditions

Interventions

TypeNameDescription
DRUGExtended Release FlucytosineGiven PO
DEVICENovoTTF-100A DeviceReceive Optune device
OTHERQuality-of-Life AssessmentAncillary studies
OTHERQuestionnaire AdministrationAncillary studies
RADIATIONRadiation TherapyUndergo radiation
DRUGTemozolomideGiven PO
PROCEDURETherapeutic Conventional SurgeryUndergo standard of care surgery
BIOLOGICALVocimagene AmiretrorepvecGiven via intracranial injection

Timeline

Start date
2020-01-31
Primary completion
2025-11-30
Completion
2030-11-30
First posted
2019-09-26
Last updated
2020-03-24

Regulatory

Source: ClinicalTrials.gov record NCT04105374. Inclusion in this directory is not an endorsement.