Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02060890
Recruitment Status : Completed
First Posted : February 12, 2014
Results First Posted : December 6, 2017
Last Update Posted : November 8, 2018
Sponsor:
Collaborators:
Translational Genomics Research Institute
The Ben & Catherine Ivy Foundation
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Nicholas Butowski, University of California, San Francisco

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
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.

Layout table for study information
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 : August 2014
Actual Primary Completion Date : September 3, 2015
Actual Study Completion Date : May 10, 2017

Resource links provided by the National Library of Medicine


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 Name: standard of care therapy




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. 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.

  2. 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.


Biospecimen Retention:   Samples With DNA

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients presenting with recurrent or progressive glioblastoma that are eligible for surgical resection.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02060890


Locations
Layout table for location information
United States, California
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
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Michael Prados, MD University of California, San Francisco

Layout table for additonal information
Responsible Party: Nicholas Butowski, Professor, Neuro-Oncology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02060890     History of Changes
Other Study ID Numbers: CC14101
NCI-2017-00467 ( Registry Identifier: CTRP (Clinical Trial Reporting Program )
P30CA082103 ( U.S. NIH Grant/Contract )
First Posted: February 12, 2014    Key Record Dates
Results First Posted: December 6, 2017
Last Update Posted: November 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No

Keywords provided by Nicholas Butowski, University of California, San Francisco:
Glioblastoma

Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue