Adult Glioblastoma
Conditions
Keywords
Glioblastoma
Brief summary
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.
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.
Interventions
feasibility of a specialized tumor board to come up with treatment recommendations no later than 35 days from surgery.
Sponsors
Translational Genomics Research Institute
The Ben & Catherine Ivy Foundation
University of California, San Francisco
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received Treatment Recommendations Within 35 Days of Surgery | 35 days from surgery to making genomic informed treatment recommendation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Chose to Pursue Treatment | Within 35 days from surgery to making genomic informed treatment recommendation | Number of patients who chose to pursue treatment based on these genomics-informed treatment recommendations |
Other
| Measure | Time frame | Description |
|---|---|---|
| Successful Generation of Patient-derived Xenograft (PDX) Genomic Models | Within 12 months after tissue collection | Number of patient-derived xenograft (PDX) models successfully derived from patient tumor samples. |
| Number of Participants Reaching 12 Months Progression Free Survival | 12 month progression free survival | Treatment efficacy derived from specialized Tumor Board suggestion, defined by 12 month progression free survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
specialized tumor board recommendation: feasibility of a specialized tumor board to come up with treatment recommendations no later than 35 days from surgery. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Group A |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 2 / 7 |
Outcome results
Primary
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.
Time frame: 35 days from surgery to making genomic informed treatment recommendation
Population: 16 pts had tumor tissue for analysis; 15 of 16 patients received treatment recommendations within 35 days of surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Participants Who Received Treatment Recommendations Within 35 Days of Surgery | 15 Participants |
Secondary
Number of Patients Who Chose to Pursue Treatment
Number of patients who chose to pursue treatment based on these genomics-informed treatment recommendations
Time frame: Within 35 days from surgery to making genomic informed treatment recommendation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Patients Who Chose to Pursue Treatment | 7 Participants |
Other Pre-specified
Number of Participants Reaching 12 Months Progression Free Survival
Treatment efficacy derived from specialized Tumor Board suggestion, defined by 12 month progression free survival.
Time frame: 12 month progression free survival
Population: Number of patients who chose to pursue treatment based on genomic informed recommendations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Participants Reaching 12 Months Progression Free Survival | 2 Participants |
Other Pre-specified
Successful Generation of Patient-derived Xenograft (PDX) Genomic Models
Number of patient-derived xenograft (PDX) models successfully derived from patient tumor samples.
Time frame: Within 12 months after tissue collection
Population: Nine patients had sufficient tissue sent for PDX model development.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Successful Generation of Patient-derived Xenograft (PDX) Genomic Models | 5 Participants |