Evaluation of ex Vivo Drug Combination Optimization Platform in Recurrent High Grade Astrocytic Glioma

Launched by NATIONAL UNIVERSITY HOSPITAL, SINGAPORE · Sep 4, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at how to find the best drug combinations for patients with recurrent high-grade astrocytic gliomas, a type of brain tumor. Researchers will take samples of brain tumor tissue from patients and grow them in the lab to create mini-tumors called organoids. These organoids will then be tested with different drugs to see which combinations work best for treating the patient's specific tumor. The idea is that these organoids can closely mimic how the actual tumor behaves, helping doctors to choose the most effective treatment options.

To participate in this trial, patients need to be 21 years or older and have a confirmed diagnosis of high-grade astrocytic glioma. They should have already undergone initial treatment, which includes surgery followed by standard chemotherapy and radiation. Patients must also have enough tumor tissue available for testing and be in good overall health. During the trial, participants will have their tumor samples analyzed to help determine the best treatment strategy for their condition. It's important for potential participants to discuss this opportunity with their healthcare provider to see if they meet the requirements and if it could be a suitable option for them.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Pre-screening:
• • 1. Patients 21 years of age or older, with ECOG performance status 0 to 2, and with a life expectancy of more than 3 months with suspected high grade astrocytic glioma, fit for treatment comprising standard-of-care therapy with adjuvant temozolomide and radiotherapy if the diagnosis of high grade astrocytoma is pathologically confirmed.
• • 2. Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.
• • Patients will be enrolled at the time of initial surgery but study imaging and further PDO generation will not take place if the patient is subsequently found not to meet the histological criteria or will not be receiving standard adjuvant temozolomide/ radiotherapy.
• All subsequent criteria apply to the main study only:
• • 1. Patients 21 years of age or older, with ECOG performance status 0 to 2, and life expectancy of more than 3 months with pathologically confirmed high grade astrocytic glioma, having undergone first-line standard-of-care therapy with surgery/biopsy followed by temozolomide and radiotherapy. Subjects with truncated adjuvant chemoradiotherapy may be enrolled at the Principal Investigator's discretion.
• • 2. Documented tumor progression based on standard clinical, radiological or histological criteria, and deemed suitable for second line systemic therapy.
• • 3. Sufficient tumor tissue available for PDO generation at baseline and at least one available or pending QPOP result.
• 4. Adequate organ function as defined by:
• • 1. Bone marrow function i. Haemoglobin ≥ 9g/dl ii. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii. Platelet count ≥ 100 x 109/L. 2. Liver function i. Bilirubin \< 2.5x upper limit of normal (ULN) ii. Alanine transaminase (ALT) and aspartate transaminase (AST) \< 2.5x ULN or \< 5x ULN if liver metastases are present iii. Prothrombin time (PT) within the normal range for the institution. 3. Renal function i. Plasma creatinine \<1.5x institutional ULN 5) Capable of swallowing tablets. 6) Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
• • Exclusion Criteria (both pre-screening/ main study)
• • 1. Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 2 weeks of study entry.
• • 2. Pregnancy or breastfeeding at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential must have a negative pregnancy test at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) while on anti-cancer treatment and until at least 3 months after the last study drug administration.
• • 3. Concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis \& T1) or any cancer curatively treated less than 5 years prior to study entry.
• • 4. Patients with leptomeningeal dissemination of disease and/or pure spinal high grade gliomas will be excluded.
• • 5. Kidney disease which would clinically disqualify the subject from serial MRI scans with gadolinium contrast.