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 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 pilot, single-institution, single cohort, non-randomized open-label study to assess
feasibility of implementing an individualized treatment regimen in patients with surgical
recurrent 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. We 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
repurposed 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. Treatment will continue until tumor
1. Patient age must be ≥ 18 years
2. Patients must understand and provide written informed consent and HIPAA authorization
authorization prior to initiation of any study-specific procedures
3. Patients must have recurrence of histologically-proven glioblastoma or gliosarcoma,
WHO grade IV that is surgically resectable.
4. The patient's surgeon thinks that they can resect at least 500 mg of tumor.
5. Patient must have KPS score ≥ 70
6. Patient must have an estimated life expectancy ≥ 3 months
7. Patients may enroll independent of number of prior therapies or cumulative doses of
prior therapies, but must have received appropriate prior therapy for GBM at time of
initial diagnosis, including radiation therapy.
8. Patient must have adequate bone marrow function, renal function, and hepatic function
as defined below:
Adequate bone marrow function:
1. absolute neutrophil count (ANC) ≥ 1,500/μL
2. Platelets ≥ 100,000/μL
Adequate hepatic function:
1. total bilirubin ≤ 1.5x institutional upper limit of normal
2. AST(SGOT) ≤ 2.5x institutional upper limit of normal
3. ALT(SGPT) ≤ 2.5x institutional upper limit of normal
Adequate renal function:
a. creatinine ≤ 1.5x institutional upper limit of normal OR creatinine clearance ≥ 60
9. Must be able to undergo MRI scans for tumor evaluation.
10. The effects of study drugs, either individually or their combination on the developing
human fetus are unknown. For this reason, women of child-bearing potential and men
must agree to use adequate contraception prior to study entry and for the duration of
study participation and for 3 months after completion of study drug administration.
The use of adequate contraception may be longer than 3 months depending on the drugs
used and the FDA-approved labeling in cases of recommendation for contraception.
Adequate contraception may include hormonal contraception, barrier method (condom,
contraceptive sponge, diaphragm or ring), intrauterine device (IUD), tubal ligation,
vasectomy and abstinence. Should a woman become pregnant (or suspect that she is
pregnant) while she or her partner is participating in this study, she should inform
her treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 3 months after completion of study drug administration.
11. Patients must not have New York Heart Association (NYHA) Grade II or greater
congestive heart failure
12. Patients must not have history of myocardial infarction or unstable angina within 12
months prior to study enrollment.
1. Patient who has been treated with any chemotherapy or radiotherapy ≤4 weeks prior to
date of study registration. Exceptions to this include: must be ≥ 23 days from last
dose of TMZ, must be ≥ 6 weeks from last dose of nitrosurea.
2. Patient who has not recovered to grade 1 or baseline from the adverse effects of prior
radiotherapy or chemotherapy.
3. Patient who is < 12 weeks from initial course of radiation
4. Patients with multifocal tumor, primarily infratentorial or posterior fossa tumor, or
leptomeningeal dissemination of tumor.
5. Patient with any other active alignancy besides GBM, excluding non-melanomatous skin
cancer, or carcinoma in situ of the cervix, prostate, or breast, unless patient has
been disease-free/in remission for ≥2 years prior to date of study enrollment
6. Patients known to be HIV-positive. HIV testing is not required for study
7. Uncontrolled concurrent illness including psychiatric illness, or situations that
would limit compliance with the study requirements or the ability to willingly give
written informed consent.