Clinical Trials /

Feasibility of Individualized Therapy for Recurrent GBM

NCT03681028

Description:

The current study will test the ability and likelihood of successfully implementing individualized combination treatment recommendations for adult patients with surgically-resectable recurrent glioblastoma in a timely fashion. Collected tumor tissue and blood will be examined using a new diagnostic testing called UCSF 500 Cancer Gene Panel which is done at the UCSF Clinical Cancer Genomics Laboratory. The UCSF 500 Cancer Gene Panel will help identify genetic changes in the DNA of a patient's cancer, which helps oncologists improve treatment by identifying targeted therapies.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Feasibility of Individualized Therapy for Recurrent GBM
  • Official Title: Pilot Study Testing Feasibility of Individualized Therapy for Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CC# 18108
  • SECONDARY ID: 18-24939
  • NCT ID: NCT03681028

Conditions

  • Recurrent Glioblastoma

Interventions

DrugSynonymsArms
Individualized therapyIndividualized therapy

Purpose

The current study will test the ability and likelihood of successfully implementing individualized combination treatment recommendations for adult patients with surgically-resectable recurrent glioblastoma in a timely fashion. Collected tumor tissue and blood will be examined using a new diagnostic testing called UCSF 500 Cancer Gene Panel which is done at the UCSF Clinical Cancer Genomics Laboratory. The UCSF 500 Cancer Gene Panel will help identify genetic changes in the DNA of a patient's cancer, which helps oncologists improve treatment by identifying targeted therapies.

Detailed Description

      This is a pilot, single-institution, single cohort, non-randomized open-label study to assess
      feasibility of implementing an individualized treatment regimen in patients with surgical
      recurrent GBM. Patients are not stratified according to demographic or treatment-related
      parameters. Patients must have recurrent glioblastoma treated with appropriate tumor
      treatment including radiation therapy at initial diagnosis. Surgery must be clinically
      indicated and patients must be candidates for tumor resection at UCSF.

      The goal of the current study is to build upon prior results by confirming the feasibility of
      actually implementing patient-specific drug regimens in a rapid, clinically-relevant
      timetable. We will also assess for efficacy, safety, and response outcomes of these
      patient-specific regimens, to generate preliminary data that would support a larger trial
      assessing efficacy of such an approach.

      Resected tumor tissue and blood will be examined using Next Generation Sequencing (NGS) UCSF
      500 Cancer Gene Panel at the UCSF Clinical Cancer Genomics Laboratory and Whole genome and
      RNA sequencing. The clinical report generated from the NGS UCSF 500 panel will be provided to
      a study-specific Tumor Board who will generate an individualized treatment recommendation
      based on the report. The individualized treatment regimen potentially will include up to 4
      repurposed off-the-shelf FDA-approved targeted agents. The Board will identify the
      expected/anticipated drug-drug interactions and anticipated additional toxicities of the
      combination of therapies. The treating physician is given the report, discusses the suggested
      treatment options with the patient, and initiates treatment, ideally within 28 calendar days
      (and no later than 35 calendar days) after surgery. Treatment will continue until tumor
      progression.
    

Trial Arms

NameTypeDescriptionInterventions
Individualized therapyOtherStudy treatment for a given patient will consist of a regimen chosen from agents implicated in critical molecular signaling pathways and/or from signature-based predictions of drug efficacy. All agents are listed in the current pharmacopoeia for human use, but will differ amongst individual subjects. The study treatment will consist of up to 4 FDA approved drugs that have known dosing. This study is not only looking at 4 drugs. It is selecting up to 4 drugs per patient but the drugs chosen can be any FDA-approved drug. Therefore, it is not possible to pre-specify the medications.
  • Individualized therapy

Eligibility Criteria

        Inclusion Criteria:

          1. Patient age must be ≥ 18 years

          2. Patients must understand and provide written informed consent and HIPAA authorization
             authorization prior to initiation of any study-specific procedures

          3. Patients must have recurrence of histologically-proven glioblastoma or gliosarcoma,
             WHO grade IV that is surgically resectable.

          4. The patient's surgeon thinks that they can resect at least 500 mg of tumor.

          5. Patient must have KPS score ≥ 70

          6. Patient must have an estimated life expectancy ≥ 3 months

          7. Patients may enroll independent of number of prior therapies or cumulative doses of
             prior therapies, but must have received appropriate prior therapy for GBM at time of
             initial diagnosis, including radiation therapy.

          8. Patient must have adequate bone marrow function, renal function, and hepatic function
             as defined below:

             Adequate bone marrow function:

               1. absolute neutrophil count (ANC) ≥ 1,500/μL

               2. Platelets ≥ 100,000/μL

             Adequate hepatic function:

               1. total bilirubin ≤ 1.5x institutional upper limit of normal

               2. AST(SGOT) ≤ 2.5x institutional upper limit of normal

               3. ALT(SGPT) ≤ 2.5x institutional upper limit of normal

             Adequate renal function:

             a. creatinine ≤ 1.5x institutional upper limit of normal OR creatinine clearance ≥ 60
             mL/min/1.73 m2

          9. Must be able to undergo MRI scans for tumor evaluation.

         10. The effects of study drugs, either individually or their combination on the developing
             human fetus are unknown. For this reason, women of child-bearing potential and men
             must agree to use adequate contraception prior to study entry and for the duration of
             study participation and for 3 months after completion of study drug administration.
             The use of adequate contraception may be longer than 3 months depending on the drugs
             used and the FDA-approved labeling in cases of recommendation for contraception.
             Adequate contraception may include hormonal contraception, barrier method (condom,
             contraceptive sponge, diaphragm or ring), intrauterine device (IUD), tubal ligation,
             vasectomy and abstinence. Should a woman become pregnant (or suspect that she is
             pregnant) while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 3 months after completion of study drug administration.

         11. Patients must not have New York Heart Association (NYHA) Grade II or greater
             congestive heart failure

         12. Patients must not have history of myocardial infarction or unstable angina within 12
             months prior to study enrollment.

        Exclusion Criteria:

          1. Patient who has been treated with any chemotherapy or radiotherapy ≤4 weeks prior to
             date of study registration. Exceptions to this include: must be ≥ 23 days from last
             dose of TMZ, must be ≥ 6 weeks from last dose of nitrosurea.

          2. Patient who has not recovered to grade 1 or baseline from the adverse effects of prior
             radiotherapy or chemotherapy.

          3. Patient who is < 12 weeks from initial course of radiation

          4. Patients with multifocal tumor, primarily infratentorial or posterior fossa tumor, or
             leptomeningeal dissemination of tumor.

          5. Patient with any other active alignancy besides GBM, excluding non-melanomatous skin
             cancer, or carcinoma in situ of the cervix, prostate, or breast, unless patient has
             been disease-free/in remission for ≥2 years prior to date of study enrollment

          6. Patients known to be HIV-positive. HIV testing is not required for study
             participation.

          7. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of implementing a truly personalized tumor treatment drug regimen for patients with surgically resectable recurrent glioblastoma
Time Frame:Within 35 days of surgery
Safety Issue:
Description:Percentage of patients who have successfully initiated therapy based on their individualized treatment regimen within 35 days following surgical resection of recurrent tumor.

Secondary Outcome Measures

Measure:Incidence of drug-related AEs, grade 3-5 using NCI CTCAE v5.0 either due to individual treatment or combination treatment regimen
Time Frame:Drug-related adverse events measured from start of individual treatment or combination treatment regimen until 30 days following administration of last study agent
Safety Issue:
Description:Incidence of drug-related AEs, grade 3-5 using NCI CTCAE v5.0 either due to individual treatment or combination treatment regimen
Measure:progression-free survival
Time Frame:Measured from initiation of drug regimen until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 5 years.
Safety Issue:
Description:PFS period is defined as the number of days from start of individual treatment or combination treatment regimen to disease progression or death. The PFS days of patient groups will be estimated using Kaplan-Meier method to show median progression-free period (days when 50% patients remain progression-free).
Measure:progression-free survival @ 6 months
Time Frame:Measured at 6 months (24 weeks) from initiation of drug regimen
Safety Issue:
Description:PFS @ 6 months is defined as the percentage of participants who have neither progressed nor died within 6 months after the first dose of individual treatment or combination treatment regimen. PFS @ 6 months will be assessed by (modified) RANO. PFS-6 will be estimated using Kaplan Meier method.
Measure:Overall survival
Time Frame:Determined from start of individual treatment or combination treatment regimen to date of death, assessed up to 5 years.
Safety Issue:
Description:Overall survival is defined as the length of time from start of individual treatment or combination treatment regimen until date of death. For the participants who were alive at the end of study or lost to follow-up, overall survival will be censored on the last date when participants were known to be alive. OS will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jennifer Clarke

Trial Keywords

  • Glioblastoma
  • Adult Glioblastoma
  • Glioma
  • Precision Medicine
  • Specialized Tumor Board

Last Updated

November 14, 2018