Pilot Study Testing Feasibility of Individualized Therapy for Recurrent Glioblastoma
Overview
- Phase
- Phase 1
- Intervention
- Individualized therapy
- Conditions
- Recurrent Glioblastoma
- Sponsor
- Jennifer Clarke
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Overall survival at 9 months (OS)
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Jennifer Clarke
Associate Professor
University of California, San Francisco
Eligibility Criteria
Inclusion Criteria
- •Patient age must be \>= 18 years
- •Patients must understand and provide written informed consent and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization authorization prior to initiation of any study-specific procedures
- •Patients must have recurrence of histologically-proven glioblastoma or gliosarcoma, World Health Organization (WHO) grade IV that is surgically resectable.
- •The patient's surgeon thinks that they can resect at least 500 mg of tumor.
- •Patient must have Karnofsky Performance Scale (KPS) score \>=70
- •Patient must have an estimated life expectancy ≥ 3 months
- •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.
- •Patient must have adequate bone marrow function, renal function, and hepatic function as defined below:
- •Adequate bone marrow function:
- •absolute neutrophil count (ANC) \>= 1,500/μL
Exclusion Criteria
- •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 temozolomide (TMZ), must be ≥ 6 weeks from last dose of nitrosurea.
- •Patient who has not recovered to grade 1 or baseline from the adverse effects of prior radiotherapy or chemotherapy.
- •Patient who is \< 12 weeks from initial course of radiation
- •Patients with multifocal tumor, primarily infratentorial or posterior fossa tumor, or leptomeningeal dissemination of tumor.
- •Patient with any other active malignancy 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
- •Patients known to be HIV-positive. HIV testing is not required for study participation.
- •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.
- •Any other acute or chronic medical or psychiatric condition, or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results, and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
Arms & Interventions
Individualized therapy
Study treatment for a given patient will consist of a regimen chosen from agents implicated in critical molecular signaling pathways and/or from signature-based predictions of drug efficacy. All agents are listed in the current pharmacopoeia for human use, but will differ amongst individual subjects. The study treatment will consist of up to 4 FDA approved drugs that have known dosing. This study is not only looking at 4 drugs. It is selecting up to 4 drugs per patient but the drugs chosen can be any FDA-approved drug. Therefore, it is not possible to pre-specify the medications.
Intervention: Individualized therapy
Outcomes
Primary Outcomes
Overall survival at 9 months (OS)
Time Frame: Up to 9 months
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.
Percentage of patients who have successfully initiated therapy
Time Frame: Up to 35 days after surgery
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.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to 5 years.)
- Incidence of treatment-related Adverse Events (AEs)(Up to 1 year)
- Progression-Free Survival (PFS) at 6 months(6 months)
- Time to Treatment Failure (TTF)(Up to 5 years)
- Overall survival (OS)(Up to 5 years)