SHS_571008 COBC NSWE 15221
A Phase 0/1 Study of Combination Drug Therapy For Glioblastoma Based on Personalized Cancer Stem Cell (CSC) High-Throughput Drug Screening (HTS)
A study to determine the safety of CSC/ HTS-based combination drug therapy in subjects who have GBM that has recurred or progressed following prior radiation therapy and TMZ. This protocol describes a prospective single-center Phase 0/1 open-label study to evaluate the safety and efficacy of a high-throughput drug sensitivity assay to predict targeted therapies for patients who have GBM that has recurred or progressed following prior radiation therapy and TMZ. The underlying hypothesis is that treatment of patients with up to 3 lead candidates identified from individualized CSC/ HTS assays will safely (1) delay disease progression, and (2) increase survival. There is an abundance of literature strongly supporting the importance of a regimen for targeting CSCs and preventing tumor recurrence, as an additional strategy to improve the overall prognosis of cancer patients.
Select Inclusion Criteria:
Histological diagnosis of GBM [WHO grade IV].
Subjects ≥18 years of age
Patients must have a life expectancy of >12 weeks
Surgically accessible tumor with the intent for a gross or near total resection of the tumor mass (GBM, WHO grade IV)
Collection of sufficient tumor material for processing CSCs
Disease progression following radiation and TMZ therapy (as defined by RANO criteria (45); Appendix 3). Unlimited relapses are allowed provided the functional status and other eligibility criteria for enrollment are met.
Must have a KPS rating of ≥70
Must have recovered from the toxic effects of prior therapy to < Grade 2 toxicity per NCI CTCAE version 4 (Appendix 6) prior to Day 1 of Cycle 1.
Adequate renal, hepatic and bone marrow function based on screening laboratory assessments.
Any condition, including the presence of clinically significant laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)
Inadequately controlled hypertension
New York Heart Association (NYHA) Grade II or greater congestive heart failure
History of myocardial infarction or unstable angina within 6 months
History of stroke or transient ischemic attack within 6 months
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month.
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
Grade 2 or higher peripheral neuropathy per NCI CTCAE version 4
History of abdominal fistula or gastrointestinal (GI) perforation within 6 months.
Serious, non-healing wound, active ulcer, or untreated bone fracture
Allergies to reagents used in this study
Women of child bearing age not willing to use a reliable form of contraception
Pregnancy (positive pregnancy test) or lactation
Patient is positive for HIV, Hepatitis B or C
Concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) Patients must discontinue an EIAED at least two weeks prior to starting study drug
Concurrent use of herbal medications
Patient is simultaneously participating in another clinical trial during the Phase 1 (treatment phase) of this study. Patients may enroll/consent in the Phase 0 portion of this study for tissue collection and HTS while being treated with standard of care or clinical trial for newly diagnosed GBM prior to recurrence.
Charles Cobbs, M.D.
Swedish Medical Center