Molecular Profiling in Guiding Individualized Treatment Plan in Adults With Recurrent/Progressive Glioblastoma (TGEN)

A Pilot Trial Testing the Feasibility of Using Molecular Profiling to Guide an Individualized Treatment Plan in Adults With Recurrent/Progressive Glioblastoma

This current study will use a new treatment approach based on each patient's tumor genomic profiling consisting of whole genome sequencing, exome analysis, and RNA sequencing as well as predictive modeling. This new treatment strategy has shown promising results in adult patients with other solid tumors.

Study Overview

• Status: Completed
• Conditions: Adult Glioblastoma
• Intervention / Treatment: Other: specialized tumor board recommendation

Detailed Description

Patients with recurrent glioblastoma who are candidates for surgery for their clinical management will have tumor tissue taken at the time of surgery. Tissue samples will be obtained from the contrasting edge as well as infiltrating margins. Circulating tumor DNA will also be taken from blood samples before, and after surgery and every 2 months. Genomic profiling of the tumor tissue will be performed and a Molecular Tumor Board will review the profiling within 28 to 35 days of surgery. If specific potential targets are amenable to treatment, a treatment recommendation will be made. Up to 4 drugs could be suggested to the treating physician. The patient and the treating physician may or may not choose to use the recommendation. Any drug from the US Pharmacopeia may be chosen. If the treatment as suggested is given, patients will be followed for toxicity and efficacy, including progression and survival. If the treatment is not given, patients will be followed for progression and survival.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients presenting with recurrent or progressive glioblastoma that are eligible for surgical resection.

Description

Inclusion Criteria:

• Patients must understand and provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to initiation of any study-specific procedures
• Have a life expectancy of at least 3 months
• Patients must have a diagnosis of histologically confirmed Glioblastoma that is felt on imaging to be progressive despite standard of care treatment
• at least 18 years of age
• Patient is a good medical candidate for a standard of care surgical procedure
• Patients may enroll independent of number of prior therapies, but must have received prior radiation therapy
• Patients must have a performance status (KPS) of at least 60.

Exclusion Criteria:

• 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

Eligibility for treatment using the specialized Tumor Board recommendations

• Patients must have fully recovered from any toxicity associated with surgery
• Must begin treatment no longer than 35 calendar days from surgery
• Must have KPS at least 60
• Must have Absolute Neutrophil Count (ANC) at least 1500/mm3, platelets at least 125,000/mm2, Hg at least 8 gm/dl
• Must have electrolytes (Na, K, Co2, Cl) within normal limits using institutional guidelines
• Must have baseline MRI within 14 days prior to starting cycle 1, day 1 of treatment (+/- 3 days)
• Additional laboratory guidelines will be based upon therapies suggested by the specialized Tumor Board based upon anticipated, known toxicities of those agents and must be within at least 1.5 x upper normal limits of institutional normal limits
• Patient must agree to follow the recommended treatment regimen, including clinic visits, laboratory, imaging, and toxicity assessments

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group A; Patients will undergo collection of tumor at the time of tumor resection and after confirmation of tumor progression and will have blood samples drawn pre-surgery and during standard of care follow-up visits. Patients will then be provided with a specialized tumor board recommendations for personalized treatment options for up to 4 medications based on the specimen analysis results within 35 days of surgery. Patients may then elect to initiate recommended therapy within 42 days of surgery.

Other: specialized tumor board recommendation; feasibility of a specialized tumor board to come up with treatment recommendations no later than 35 days from surgery.; Other Names: standard of care therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Received Treatment Recommendations Within 35 Days of Surgery	To demonstrate feasibility, we would want the treatment recommendation to be fully complete within 35 calendar days in at least 85% of patients for which sufficient RNA and DNA is available.	35 days from surgery to making genomic informed treatment recommendation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Who Chose to Pursue Treatment	Number of patients who chose to pursue treatment based on these genomics-informed treatment recommendations	Within 35 days from surgery to making genomic informed treatment recommendation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Generation of Patient-derived Xenograft (PDX) Genomic Models	Number of patient-derived xenograft (PDX) models successfully derived from patient tumor samples.	Within 12 months after tissue collection
Number of Participants Reaching 12 Months Progression Free Survival	Treatment efficacy derived from specialized Tumor Board suggestion, defined by 12 month progression free survival.	12 month progression free survival

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Translational Genomics Research Institute; The Ben & Catherine Ivy Foundation
• Investigators: Principal Investigator: Michael Prados, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): September 3, 2015
• Study Completion (Actual): May 10, 2017

Study Registration Dates

• First Submitted: February 7, 2014
• First Submitted That Met QC Criteria: February 10, 2014
• First Posted (Estimated): February 12, 2014

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Glioblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: CC14101; NCI-2017-00467 (Registry Identifier: CTRP (Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No