Individualized Therapy in Treating Patients with Recurrent Resectable Glioblastoma or Gliosarcoma
This phase I trial studies how well individualized therapy works in treating patients with glioblastoma or gliosarcoma that has come back and can be removed by surgery. Creating a patient-specific tumor genomic profile to make an individualized treatment plan may be more effective in treating patients with glioblastoma or gliosarcoma.
Inclusion Criteria
- Patient age must be >= 18 years
- 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
- Patients must have recurrence of histologically-proven glioblastoma or gliosarcoma, World Health Organization (WHO) grade IV that is surgically resectable
- The patient’s surgeon thinks that they can resect at least 500 mg of tumor
- Patient must have Karnofsky performance status (KPS) score >= 70
- Patient must have an estimated life expectancy >= 3 months
- 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
- Absolute neutrophil count (ANC) >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< 1.5 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2
- Must be able to undergo magnetic resonance imaging (MRI) scans for tumor evaluation
- Women of child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to surgery * 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 Food and Drug Administration (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. Patient must not be a woman who is currently pregnant, due to the potential for teratogenic or abortifacient effects of study drugs, either alone or in combination. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, lactating women who are breastfeeding should discontinue breastfeeding if the mother is treated with any study drug
- Patients must not have New York Heart Association (NYHA) grade II or greater congestive heart failure
- Patients must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment
Exclusion Criteria
- 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 temozolomide (TMZ), must be >= 6 weeks from last dose of nitrosurea
- Patient who has not recovered to grade 1 or baseline from the adverse effects of prior radiotherapy or chemotherapy
- Patient who is < 12 weeks from initial course of radiation
- Patient with multifocal tumor, primarily infratentorial or posterior fossa tumor, or leptomeningeal dissemination of tumor
- Patient with any other active malignancy 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
- Patients known to be human immunodeficiency virus (HIV)-positive. HIV testing is not required for study participation
- 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
- Any other acute or chronic medical or psychiatric condition, or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results, and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03681028.
PRIMARY OBJECTIVES:
I. Feasibility of initiation of a patient-specific tumor-treatment regimen within 35 days following surgical resection of recurrent glioblastoma (GBM). (Initial Cohort)
II. Overall survival. (Combined Initial and Expansion Cohorts)
SECONDARY OBJECTIVES:
I. Safety of individualized treatment combination regimen. (Combined Initial and Expansion Cohorts)
II. Efficacy of individualized treatment combination regimen with regard to response, progression-free survival and overall survival. (Combined Initial and Expansion Cohorts)
EXPLORATORY OBJECTIVES:
I. To compare more extensive whole genome and ribonucleic acid (RNA) sequencing analysis of the tumor to the standard University of California San Francisco (UCSF) 500 gene panel with respect to identification of therapeutic targets.
II. To compare UCSF500, whole genome and RNA sequencing results between enhancing and nonenhancing tumor.
III. To generate preclinical models that may serve for non-invasive testing of selected agents and correlation with patient outcome.
IV. To evaluate the role of advanced imaging using hyperpolarized 13C techniques in assessing early response to treatment.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
INITIAL COHORT: Within 21-28 days after surgery, patients receive individualized therapy. Cycles repeat every 3 or 4 weeks in the absence of disease progression or unacceptable toxicity.
EXPANSION COHORT:
Within 21-28 days after surgery, patients receive individualized therapy. Treatment consists of a drug which kills rapidly dividing cells (“cytotoxic”) plus up to 2 drugs that target a particular pathway in the growth of cancer cells or stimulates the immune system to fight cancer (“targeted agents”). Cycles repeat every 3 or 4 weeks in the absence of disease progression or unacceptable toxicity.
* Expansion cohort patients positive for MGMT promoter methylation without a high number of mutations receive the drugs temozolomide and olaparib. Patients negative for MGMT promoter methylation OR a high number of mutations regardless of methylation status AND have never received a type of drug called a nitrosourea receive the drug lomustine. Patients whose tumor meets either of these criteria but previously received a type of
drug called a nitrosourea receive the drug carboplatin instead.
* Expansion cohort patients with a change in the EGFR gene may also receive the drug afatinib.
* If 2 targeted agents have not already been assigned, expansion cohort patients with:
** Any deletions in the CDKN2A/B genes may also receive the drug abemaciclib.
** Tumor shows an increased number of copies of the CDK4 gene may also receive the drug abemaciclib.
** Tumor shows a change in the NF1 gene may also receive the drug trametinib.
After completion of study treatment, patients are followed up for 30 days, every 3 months for the first 2 years, and then every 6 months thereafter.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationUniversity of California San Francisco
Principal InvestigatorJennifer Leigh Clarke
- Primary ID18108
- Secondary IDsNCI-2018-02194, 18-24939
- ClinicalTrials.gov IDNCT03681028