Overview

GBM Personalized Trial

Status:
Not yet recruiting
Trial end date:
2027-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Early Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AHS Cancer Control Alberta
Treatments:
Afatinib
Dasatinib
Everolimus
Olaparib
Palbociclib
Criteria
Inclusion Criteria:

1. Study participant has provided informed consent prior to initiation of any study
specific activities/procedures.

2. 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.

3. Recurrence is amenable to resection.

4. Performance status: ECOG ≤2.

5. 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.

6. 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.

7. Able to undergo brain MRIs.

8. Females must not be breastfeeding, throughout the study period up to 180 days after
the last dose of study intervention.

9. Male patients should agree to not donate sperm during the study for at least 6 months
until discontinuation of study drug.

Exclusion Criteria:

1. Patients with history of abnormal left ventricular ejection fraction (LVEF≤ 45%).

2. Pregnant, breast-feeding, unwilling/unable to comply with contraception requirements.

3. Patients unable to consent.

4. Abnormal (grade ≥2 CTCAE, version 5.0) laboratory values for hematology, renal, and
liver function including:

1. Hemoglobin <10,

2. Neutrophils <1.5,

3. Platelets <75,

4. ALT/AST >3x ULN,

5. Bilirubin >1.5 x ULN,

6. eGFR <60

5. 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).

6. Patients with a history of ILD (interstitial lung disease) must be excluded.

7. Patients with severe hepatic impairment (Child Pugh C).

8. A significantly abnormal ECG (baseline QTcF interval > 450 msec).

9. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption.

10. Patients with known pre-existing pleural effusion.

11. Active hepatitis B or C infection and/or known history of HIV infection.

12. Has known psychiatric or substance abuse disorders that would interfere with
compliance with the requirements of the trial.

13. Subject will not be available for protocol-required study visits or procedures, to the
best of the subject's and investigator's knowledge.

14. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks from the date of signing the informed consent form.

15. Patients who are hypersensitive to any ingredients in the formulation of the study
drugs or their excipients.

16. Patients receiving active treatment for a different cancer.

17. If recent bacterial infection, patients need to have completed antibiotic course prior
to commencing study drug.

18. If recent COVID-19 infection, patients must have recovered from it prior to commencing
study drug.

19. Patients on strong CYP3A/p-gp inducers (for example, carbamazepine and phenytoin).