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

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02060890
• Collaborator: Translational Genomics Research Institute (Other), The Ben & Catherine Ivy Foundation (Other)
• Enrollment: 20
• Location: 1
• Actual Duration (Months): 33.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Glioblastoma	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 Design

• Study Type: Observational
• Actual Enrollment: 20 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: A Pilot Trial Testing the Feasibility of Using Molecular Profiling to Guide an Individualized Treatment Plan in Adults With Recurrent/Progressive Glioblastoma
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Sep 3, 2015
• Actual Study Completion Date: May 10, 2017

Arms and Interventions

Arm

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco
• Translational Genomics Research Institute
• The Ben & Catherine Ivy Foundation

Investigators

• Principal Investigator: Michael Prados, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nicholas Butowski, Professor, Neuro-Oncology, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02060890
• Other Study ID Numbers: CC14101; NCI-2017-00467
• First Posted: Feb 12, 2014
• Last Update Posted: Jul 28, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Nicholas Butowski, Professor, Neuro-Oncology, University of California, San Francisco: Glioblastoma
• Additional relevant MeSH terms: Glioblastoma

Study Results

Participant Flow

Arm/Group Title	Treatment Group
Arm/Group Description	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.
Period Title: Overall Study
STARTED	20
COMPLETED	16
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Group A
Arm/Group Description	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.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 75%
>=65 years	5 25%
Sex: Female, Male (Count of Participants)
Female	7 35%
Male	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	15 75%
Unknown or Not Reported	4 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	15 75%
More than one race	0 0%
Unknown or Not Reported	5 25%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Received Treatment Recommendations Within 35 Days of Surgery
Description	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

Outcome Measure Data

Analysis Population Description

16 pts had tumor tissue for analysis; 15 of 16 patients received treatment recommendations within 35 days of surgery.

Arm/Group Title	Group A
Arm/Group Description
Measure Participants	16
Count of Participants [Participants]	15 75%

2. Secondary Outcome

Title	Number of Patients Who Chose to Pursue Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description
Measure Participants	15
Count of Participants [Participants]	7 35%

3. Other Pre-specified Outcome

Title	Successful Generation of Patient-derived Xenograft (PDX) Genomic Models
Description	Number of patient-derived xenograft (PDX) models successfully derived from patient tumor samples.
Time Frame	Within 12 months after tissue collection

Outcome Measure Data

Analysis Population Description

Nine patients had sufficient tissue sent for PDX model development.

Arm/Group Title	Treatment Group
Arm/Group Description
Measure Participants	9
Count of Participants [Participants]	5 25%

4. Other Pre-specified Outcome

Title	Number of Participants Reaching 12 Months Progression Free Survival
Description	Treatment efficacy derived from specialized Tumor Board suggestion, defined by 12 month progression free survival.
Time Frame	12 month progression free survival

Outcome Measure Data

Analysis Population Description

Number of patients who chose to pursue treatment based on genomic informed recommendations

Arm/Group Title	Treatment Group
Arm/Group Description
Measure Participants	7
Count of Participants [Participants]	2 10%

Adverse Events

Arm/Group Title	Group A
Arm/Group Description	Patients pursuing treatment after tumor board's genomics-informed treatment recommendation.
All Cause Mortality
	Group A
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Group A
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Nervous system disorders
seizure	2/7 (28.6%)	2
Respiratory, thoracic and mediastinal disorders
Lung infection	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Skin Infection	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Group A
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.