The current study will test the ability and likelihood of successfully implementing individualized combination treatment recommendations for adult patients with surgically-resectable recurrent glioblastoma in a timely fashion. Collected tumor tissue and blood will be examined using a new diagnostic testing called University of California, San Francisco (UCSF) 500 Cancer Gene Panel which is done at the UCSF Clinical Cancer Genomics Laboratory. The UCSF 500 Cancer Gene Panel will help identify genetic changes in the DNA of a patient's cancer, which helps oncologists improve treatment by identifying targeted therapies.
This is a single arm, non-randomized open-label study to assess feasibility of implementing an individualized treatment regimen in patients with surgical recurrent glioblastoma (GBM). Patients are not stratified according to demographic or treatment-related parameters. Patients must have recurrent glioblastoma treated with appropriate tumor treatment including radiation therapy at initial diagnosis. Surgery must be clinically indicated and patients must be candidates for tumor resection at UCSF. The goal of the current study is to build upon prior results by confirming the feasibility of actually implementing patient-specific drug regimens in a rapid, clinically-relevant timetable. The investigators will also assess for efficacy, safety, and response outcomes of these patient-specific regimens, to generate preliminary data that would support a larger trial assessing efficacy of such an approach. Resected tumor tissue and blood will be examined using Next Generation Sequencing (NGS) UCSF 500 Cancer Gene Panel at the UCSF Clinical Cancer Genomics Laboratory and Whole genome and RNA sequencing. The clinical report generated from the NGS UCSF 500 panel will be provided to a study-specific Tumor Board who will generate an individualized treatment recommendation based on the report. The individualized treatment regimen potentially will include up to 4 re-purposed, off-the-shelf, FDA-approved targeted agents. The Board will identify the expected/anticipated drug-drug interactions and anticipated additional toxicities of the combination of therapies. The treating physician is given the report, discusses the suggested treatment options with the patient, and initiates treatment, ideally within 28 calendar days (and no later than 35 calendar days) after surgery. Patients may continue treatment until tumor progression, intolerable side effects, or patient/physician choice to discontinue.
Study Type
INTERVENTIONAL
Allocation
1. For a given proposed individualized combination of drugs the first priority to establish doses will be to identify the same combination of drugs in a peer-reviewed journal article or presented as a reviewed abstract. 2. When a proposed individualized combination of drugs has not previously been reported, the process to establish doses will be to then identify individual members of the proposed combination that have been used in combination with other cytotoxic agents similar to those being considered for combination therapy. 3. When a proposed individualized combination of drugs has no available combination data, dosing guidelines will start with the FDA-approved package insert recommended dose.
University of California San Francisco
San Francisco, California, United States
Percentage of patients who have successfully initiated therapy
Feasibility of implementing a truly personalized tumor treatment drug regimen for patients with surgically resectable recurrent glioblastoma is defined as the percentage of patients who have successfully initiated therapy based on their individualized treatment regimen within 35 days following surgical resection of recurrent tumor.
Time frame: Up to 35 days after surgery
Overall survival at 9 months (OS)
Overall survival is defined as the length of time from start of individual treatment or combination treatment regimen until 270 days, or 9 months. For the participants who were alive at the end of study or lost to follow-up, overall survival will be censored on the last date when participants were known to be alive. OS will be estimated using the Kaplan-Meier method.
Time frame: Up to 9 months
Incidence of treatment-related Adverse Events (AEs)
Incidence of treatment-related AEs, grades 3-5 using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 either due to individual treatment or combination treatment regimen
Time frame: Up to 1 year
Progression-Free Survival (PFS) at 6 months
PFS at 6 months is defined as the percentage of participants who have neither progressed nor died within 6 months after the first dose of individual treatment or combination treatment regimen. PFS at 6 months will be assessed by (modified) Response assessment in neuro-oncology criteria (RANO) and estimated using Kaplan Meier method.
Time frame: 6 months
Progression-Free Survival (PFS)
PFS period is defined as the number of days from start of individual treatment or combination treatment regimen to disease progression or death. The PFS days of patient groups will be estimated using Kaplan-Meier method to show median progression-free period (days when 50% patients remain progression-free).
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NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Time frame: Up to 5 years.
Time to Treatment Failure (TTF)
Time to treatment failure is defined as the time from start of treatment to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.
Time frame: Up to 5 years
Overall survival (OS)
Overall survival is defined as the length of time from start of individual treatment or combination treatment regimen until date of death. For the participants who were alive at the end of study or lost to follow-up, overall survival will be censored on the last date when participants were known to be alive. OS will be estimated using the Kaplan-Meier method.
Time frame: Up to 5 years