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

• ClinicalTrials.gov Identifier: NCT02060890
• Recruitment Status: Completed
• First Posted: February 12, 2014
• Results First Posted: December 6, 2017
• Last Update Posted: July 28, 2020
• Sponsor: University of California, San Francisco
• Collaborators: Translational Genomics Research Institute; The Ben & Catherine Ivy Foundation
• Information provided by (Responsible Party): Nicholas Butowski, University of California, San Francisco

Tracking Information

• First Submitted Date: February 7, 2014
• First Posted Date: February 12, 2014
• Results First Submitted Date: June 1, 2017
• Results First Posted Date: December 6, 2017
• Last Update Posted Date: July 28, 2020
• Actual Study Start Date: August 2014
• Actual Primary Completion Date: September 3, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2017)

Number of Participants Who Received Treatment Recommendations Within 35 Days of Surgery [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 10, 2014)

Feasibility [ Time Frame: 12 Months ]

Feasibility of a specialized Tumor Board making individualized treatment recommendations within 35 calendar days of tumor tissue collection

Current Secondary Outcome Measures (submitted: November 28, 2017)

Number of Patients Who Chose to Pursue Treatment [ Time Frame: 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

Original Secondary Outcome Measures (submitted: February 10, 2014)

Treatment plan comparison [ Time Frame: 35 days ]

Treatment plans derived from tumor tissue taken from the "edge" of the enhancing disease vs. from the tumor "core" from the same patient.

Current Other Pre-specified Outcome Measures (submitted: October 10, 2018)

• Successful Generation of Patient-derived Xenograft (PDX) Genomic Models [ Time Frame: 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 [ Time Frame: 12 month progression free survival ]
  Treatment efficacy derived from specialized Tumor Board suggestion, defined by 12 month progression free survival.

Original Other Pre-specified Outcome Measures (submitted: February 10, 2014)

• Tumor markers [ Time Frame: 12 months ]
  Frequency with which unique tumor markers can be detected in the blood circulation and correlation with disease burden and response
• Xenograph genomics [ Time Frame: 12 months ]
  Genomic fidelity (to the patient's original tumor) in patient-derived xenograft (PDX) models derived from these patients
• Efficacy [ Time Frame: 12 months ]
  Efficacy of treatment plan derived from specialized Tumor Board suggestion

Descriptive Information

• Brief Title: Molecular Profiling in Guiding Individualized Treatment Plan in Adults With Recurrent/Progressive Glioblastoma
• Official Title: A Pilot Trial Testing the Feasibility of Using Molecular Profiling to Guide an Individualized Treatment Plan in Adults With Recurrent/Progressive 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.
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Surgery is done and a "core" specimen (from the enhancing component of tumor) and one or more tissue biopsies of the surrounding "rim" are obtained and processed for shipment to TGen for NGS and transcriptome profiling.

Blood is obtained prior to and 24 hours following surgery for assessment of any circulating tumor DNA in blood.

Blood for circulating tumor DNA is collected every 28 days (+/- 7 days).

Whole blood samples will be immediately sent to Ashion for extraction of DNA. Isolated DNA will be quantitated by spectrophotometry, and the distribution of molecular weights in the preparations will be visualized by gel electrophoresis. Blood derived DNA samples will be aliquoted and kept at Ashion at -20 degrees Celsius until use in molecular studies

• Sampling Method: Probability Sample
• Study Population: Patients presenting with recurrent or progressive glioblastoma that are eligible for surgical resection.
• Condition: Adult Glioblastoma

Intervention

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 Name: standard of care therapy

Study Groups/Cohorts

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.

Intervention: Other: specialized tumor board recommendation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 27, 2016): 20
• Original Estimated Enrollment (submitted: February 10, 2014): 15
• Actual Study Completion Date: May 10, 2017
• Actual Primary Completion Date: September 3, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02060890
• Other Study ID Numbers: CC14101; NCI-2017-00467 ( Registry Identifier: CTRP (Clinical Trial Reporting Program )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Nicholas Butowski, University of California, San Francisco
• Original Responsible Party: Michael Prados, University of California, San Francisco, Professor in Residence of Neurological Surgery, Charles B. Wilson MD Endowed Chair
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current

Collaborators

• Translational Genomics Research Institute
• The Ben & Catherine Ivy Foundation

Investigators

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

• PRS Account: University of California, San Francisco
• Verification Date: July 2020