Pilot Trial for Treatment of Recurrent Glioblastoma

Inclusion Criteria:

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

2. Adult participants, male and female, aged ≥18 who have a pathologically confirmedIDH-wild type glioblastoma, with first or second progression of the tumor, afterinitial 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 hasexperienced menarche and who has not undergone surgical sterilization (hysterectomyor 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 theabsence of other biological or physiological causes.

6. Patients of childbearing potential must adhere to the contraception requirement fromscreening throughout the study period up to 180 days after the last dose of studyintervention. Women/men of childbearing potential must have agreed to use two highlyeffective contraceptive methods. In addition to routine contraceptive methods suchas condom use, oral contraceptive, intrauterine device (IUD), intrauterinehormone-releasing system (IUS), "effective contraception" also includes heterosexualcelibacy and surgery intended to prevent pregnancy (or with a side-effect ofpregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateraltubal ligation, or vasectomy/vasectomized partner. However, if at any point apreviously celibate patient chooses to become heterosexually active during the timeperiod for use of contraceptive measures outlined in the protocol, he/she isresponsible for beginning contraceptive measures. Note: abstinence is acceptable if this is established and preferred contraceptionfor 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 afterthe last dose of study intervention.

9. Male patients should agree to not donate sperm during the study for at least 6months 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 contraceptionrequirements.

3. Patients unable to consent.

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

5. Hemoglobin <10,

6. Neutrophils <1.5,

7. Platelets <75,

8. ALT/AST >3x ULN,

9. Bilirubin >1.5 x ULN,

10. eGFR <60

11. Patients with significant or recent gastrointestinal disorders with diarrhea as amajor symptom (e.g., Crohn's disease, malabsorption or severe diarrhea of anyetiology) must be excluded from the clinical trial (Afatanib is not recommended inthis patient population).

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

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

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

15. Patients with rare hereditary problems of galactose intolerance, the Lapp lactasedeficiency or glucose-galactose malabsorption.

16. Patients with known pre-existing pleural effusion.

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

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

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

20. Is currently participating and receiving study therapy or has participated in astudy of an investigational agent and received study therapy or used aninvestigational device within 4 weeks from the date of signing the informed consentform.

21. Patients who are hypersensitive to any ingredients in the formulation of the studydrugs or their excipients.

22. Patients receiving active treatment for a different cancer.

23. If recent bacterial infection, patients need to have completed antibiotic courseprior to commencing study drug.

24. If recent COVID-19 infection, patients must have recovered from it prior tocommencing study drug.

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

N.B. Only patients receiving SOC neurosurgery in Alberta, Canada are eligible to participate in this trial.