Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma (ISM-GBM)

Individualized Systems Medicine Strategy for Targeting Cancer Stem Cells in Patients With Recurrent Glioblastoma (ISM-GBM)

A study to determine the feasibility and safety of individualized cancer stem cell targeted therapy based on high-throughput functional profiling of FDA/EMA-approved drugs in patients with GBM that has recurred or progressed following standards-of-care (RT, TMZ).

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: Personalized drug combination

Detailed Description

This protocol describes a prospective single-center phase 1 study to evaluate the feasibility and safety of a high-throughput drug sensitivity and resistance testing (HTS) platform of individualized cancer stem cells (CSC) to predict targeted therapies in patients with recurrence of GBM after standards-of-care. Secondary outcome include efficacy of drug treatment. The underlying hypotheses is that treatment of patients based on functional profiling og autologous CSCs using HTS a) is feasible within an acceptable time window for clinical translation, b) safely delay disease progression and c) increase survival. There are increasingly published literature that strongly support the importance of a targeting CSC to improve therapy and prevent tumor recurrence in GBM, as an additional strategy to improve the overall prognosis of patients.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Einar O. Vik-Mo, MD, PhD; Phone Number: +47 23074343; Email: uxvieb@ous-hf.no
• Study Contact Backup: Name: Erlend Skaga, MD, PhD; Phone Number: +47 23074915; Email: erlend.skaga@medisin.uio.no

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Einar O Vik-Mo, MD, PhD; Phone Number: +47 23074340; Email: uxvieb@ous-hf.no
    • Contact: Solveig Bringsli; Email: solbri@ous-hf.no
    • Principal Investigator: Einar O. Vik-Mo, MD, PhD
    • Sub-Investigator: Petter Brandal, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Recurrence of histologically verified glioblastoma
• Adequate biopsy to generate enough live cells to allow functional screening
• Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Must be 18 to 70 years of age
• Adequate bone marrow, liver and heart function
• Must be competent to give consent
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization Good Clinical Practice guidelines (ICH GCP), and national/local regulations.

Exclusion Criteria:

• Patients taking part in other clinical trials which could make inclusion or follow-up difficult
• Any reason why, in the opinion of the investigator, the patient should not participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients will be treated with drugs based on functional profiling of autologous tumor cells in vitro	Drug: Personalized drug combination; A personalized drug combination will be prescribed to each patient based on the functional drug screen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug screen completion and treatment initiation	The fraction of patient that can receive an individualized treatment based on drug screening. These drugs must be available for treatment and with a combined acceptable toxicity.	8 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response	Tumor response by the chosen drug combination evaluated according to the updated response assessment in neuro-oncology (RANO) criteria.	15 months from inclusion
Number of grade 3-5 adverse events	Adverse events induced by selected treatments according to NCI Common Terminology Criteria for Adverse Events.	15 months from inclusion
Overall survival	Overall survival in treated patients from time of second surgery to all-cause mortality.	15 months from inclusion
Patient reported quality of life, overall (QLQ-C30)	Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse.	15 months from inclusion
Patient reported quality of life, brain specific(QLQ-BN20)	Evaluated by Eastern Cooperative Oncology Group Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse.	15 months from inclusion

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Institute for Molecular Medicine
• Investigators: Principal Investigator: Einar O. Vik-Mo, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Skaga E, Kulesskiy E, Brynjulvsen M, Sandberg CJ, Potdar S, Langmoen IA, Laakso A, Gaal-Paavola E, Perola M, Wennerberg K, Vik-Mo EO. Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment. Clin Transl Med. 2019 Dec 30;8(1):33. doi: 10.1186/s40169-019-0253-6.
• Skaga E, Kulesskiy E, Fayzullin A, Sandberg CJ, Potdar S, Kyttala A, Langmoen IA, Laakso A, Gaal-Paavola E, Perola M, Wennerberg K, Vik-Mo EO. Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naive glioblastoma. BMC Cancer. 2019 Jun 25;19(1):628. doi: 10.1186/s12885-019-5861-4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: personalized treatment; functional screening
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: ISM-GBM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized data will regarding tumor characteristics and results of functional profiling will be made available after publishing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No