Clinical trial NCT05043701: Individualized Systems Medicine Functional Profiling for Recurrent Glioblastoma
Official title: Individualized Systems Medicine Strategy for Targeting Cancer Stem Cells in Patients With Recurrent Glioblastoma (ISM-GBM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Recurrent Glioblastoma
Keywords: functional screening
personalized treatment
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Institute for Molecular Medicine
First posted: 2021-09-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open labelled intervention study
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Drug screen completion and treatment initiation
timeFrame: 8 weeks after surgery
Secondary outcomes:
measure: Tumor response
timeFrame: 15 months from inclusion
measure: Number of grade 3-5 adverse events
timeFrame: 15 months from inclusion
measure: Overall survival
timeFrame: 15 months from inclusion
measure: Patient reported quality of life, overall (QLQ-C30)
timeFrame: 15 months from inclusion
measure: Patient reported quality of life, brain specific(QLQ-BN20)
timeFrame: 15 months from inclusion
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Einar O. Vik-Mo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.