Feasibility of Individualized Therapy for Recurrent Glioblastoma

NCT03681028 | Completed Phase 1 FDA Drug

• 2 other identifiers: 18108NCI-2018-02194
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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 University of California, San Francisco (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.

Conditions

Recurrent Glioblastoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage of patients who have successfully initiated therapy

  Feasibility of implementing a truly personalized tumor treatment drug regimen for patients with surgically resectable recurrent glioblastoma is defined as the percentage of patients who have successfully initiated therapy based on their individualized treatment regimen within 35 days following surgical resection of recurrent tumor.

  Up to 35 days after surgery

• Overall survival at 9 months (OS)

  Overall survival is defined as the length of time from start of individual treatment or combination treatment regimen until 270 days, or 9 months. 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.

  Up to 9 months

Secondary Outcomes (5)

• Incidence of treatment-related Adverse Events (AEs)

  Up to 1 year

• Progression-Free Survival (PFS) at 6 months

  6 months

• Progression-Free Survival (PFS)

  Up to 5 years.

• Time to Treatment Failure (TTF)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

Study Arms (1)

Individualized therapy

OTHER

Study 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.

Drug: Individualized therapy

Interventions

Individualized therapy DRUG

1. For a given proposed individualized combination of drugs the first priority to establish doses will be to identify the same combination of drugs in a peer-reviewed journal article or presented as a reviewed abstract. 2. When a proposed individualized combination of drugs has not previously been reported, the process to establish doses will be to then identify individual members of the proposed combination that have been used in combination with other cytotoxic agents similar to those being considered for combination therapy. 3. When a proposed individualized combination of drugs has no available combination data, dosing guidelines will start with the FDA-approved package insert recommended dose.

Individualized therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age must be \>= 18 years
• Patients must understand and provide written informed consent and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization 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 Scale (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.
• Patient must have adequate bone marrow function, renal function, and hepatic function as defined below:
• Adequate bone marrow function:
• absolute neutrophil count (ANC) \>= 1,500/μL
• Platelets \>= 100,000/μL
• Adequate hepatic function:
• total bilirubin \<= 1.5x institutional upper limit of normal
• Aspartate aminotransferase (AST) /serum glutamic-oxaloacetic transaminase (SGOT) \<= 2.5x institutional upper limit of normal
• Alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) \<= 2.5x institutional upper limit of normal

You may not qualify if:

• 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
• Patients 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 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.

Sponsors & Collaborators

• Jennifer Clarke: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Chen J, Oberheim Bush NA, Grabowsky JA, Kline C, Kroetz DL, Taylor JW, Villanueva-Meyer J, Molinaro AM, de Groot JF, Butowski NA, Tedesco M, Rabbitt J, Phillips JJ, Hervey-Jumper S, Aghi MK, Berger MS, Chang EF, Chang SM, Solomon DA, Clarke JL. A genomically-tailored multi-agent precision medicine clinical trial for adults with recurrent glioblastoma. Clin Cancer Res. 2026 Feb 6. doi: 10.1158/1078-0432.CCR-25-4080. Online ahead of print.

  PMID: 41649856 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Glioma

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jennifer Clarke, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 21, 2018
• Study Start: December 19, 2018
• Primary Completion: November 30, 2023
• Study Completion: December 31, 2024
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)