Pilot Trial for Treatment of Recurrent Glioblastoma

NCT05432518 | Recruiting Early Phase 1 DMC

• 1 other identifier: GBM-2022
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single-arm open-label prospective pilot feasibility trial recruiting 10 adult patients with recurrent glioblastoma who are assigned to receive the personalized study treatment based on the genetic profile of their recurrent GBM tumor resected at the time of surgery. It will be aimed to gather preliminary information on the study intervention and the feasibility of conducting a full-scale trial.

Conditions

Glioblastoma; Recurrent Disease; Recurrent Glioblastoma

Keywords

Glioblastoma; Recurrent Disease; Recurrent Glioblastoma; GBM

Outcome Measures

Primary Outcomes (1)

• Success rate of personalized GBM treatment based on molecular characterization of recurrent tumor

  Percentage of patients, interested in participating, consented and detected with target mutations and completed the treatment with one of the 5 study drugs

  From date of initial consent to participate to the end of follow up period (24 months)

Secondary Outcomes (4)

• Overall survival (OS)

  From date of study drug administration until date of death from any cause (approximately 24 months)

• Progression free survival (PFS)

  From date of study drug administration until date of radiographic confirmed progression (approximately 2 years)

• Quality of Life (QoL) EORTC QLQ-C30

  Baseline until the end of treatment

• Quality of Life (QoL) EORTC QLQ BN-20

  Baseline until the end of treatment

Other Outcomes (3)

• Genomic and expression profiling

  From date of initial consent to participate to end of follow up period (24 months)

• Organoid drug response

  From date of initial consent to participate to end of follow up period (24 months)

• Correlation of genomic and expression profiling of tissue and organoid with the organoid's best drug response

  From date of initial consent to participate to end of follow up period (24 months)

Study Arms (1)

Treatment

EXPERIMENTAL

Patients will receive one of the 5 study drugs based on their recurrent tumor mutation profile and their recurrent organoid response to these drugs: 1. Afatinib 2. Dasatinib 3. Palbociclib 4. Everolimus 5. Olaparib

Drug: Afatinib; Drug: Dasatinib; Drug: Palbociclib; Drug: Everolimus; Drug: Olaparib

Interventions

Afatinib DRUG

Afatinib will be administered orally at a dose of 40 mg daily in patients with EGFR amplification.

Also known as: Giotrif

Treatment

Dasatinib DRUG

Dasatinib will be administered orally at a dose of 100 mg once daily in patients with PDGFR amplification.

Also known as: Sprycel

Treatment

Palbociclib DRUG

Palbociclib will be administered orally at a dose of 125 mg once daily in patients with CDK4 and CDK6 amplification.

Also known as: Ibrance

Treatment

Everolimus DRUG

Everolimus will be administered orally at a dose of 10 mg daily in patients with PI3K/PTEN/mTOR activated pathways.

Also known as: Teva-everolimus

Treatment

Olaparib DRUG

Olaparib will be administered orally at a dose of 300 mg twice daily in patients with TP53 mutation.

Also known as: Lynparza

Treatment

Eligibility Criteria

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

You may qualify if:

• Study participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Adult participants, male and female, aged ≥18 who have a pathologically confirmed IDH-wild type glioblastoma, with first or second progression of the tumor, after initial treatment with radiation therapy and temozolomide.
• Recurrence is amenable to resection.
• Performance status: ECOG ≤2.
• Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
• Patients of childbearing potential must adhere to the contraception requirement from screening throughout the study period up to 180 days after the last dose of study intervention. Women/men of childbearing potential must have agreed to use two highly effective contraceptive methods. In addition to routine contraceptive methods such as condom use, oral contraceptive, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
• Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
• Able to undergo brain MRIs.
• Females must not be breastfeeding, throughout the study period up to 180 days after the last dose of study intervention.
• Male patients should agree to not donate sperm during the study for at least 6 months until discontinuation of study drug.

You may not qualify if:

• Patients with history of abnormal left ventricular ejection fraction (LVEF≤ 45%).
• Pregnant, breast-feeding, unwilling/unable to comply with contraception requirements.
• Patients unable to consent.
• Abnormal (grade ≥2 CTCAE, version 5.0) laboratory values for hematology, renal, and liver function including:
• Hemoglobin \<10,
• Neutrophils \<1.5,
• Platelets \<75,
• ALT/AST \>3x ULN,
• Bilirubin \>1.5 x ULN,
• eGFR \<60
• Patients with significant or recent gastrointestinal disorders with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption or severe diarrhea of any etiology) must be excluded from the clinical trial (Afatanib is not recommended in this patient population).
• Patients with a history of ILD (interstitial lung disease) must be excluded.
• Patients with severe hepatic impairment (Child Pugh C).
• A significantly abnormal ECG (baseline QTcF interval \> 450 msec).
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• Tom Baker Cancer Centre: collaborator

Study Sites (1)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

Afatinib; Dasatinib; palbociclib; Everolimus; olaparib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines; Sirolimus; Macrolides; Lactones

Study Officials

• Paula de Robles

  Arthur J.E. Child Comprehensive Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paula de Robles, MD

CONTACT

587-231-6051; paula.derobles@albertahealthservices.ca

Michelle Kan

CONTACT

michelle.kan@albertahealthservices.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, pilot, umbrella trial

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 27, 2022
• Study Start: June 27, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

CA (1)