Clinical trial NCT04219475: Predicting Response Patterns to Treatment in Glioblastoma (GBM) Patients
Official title: Predicting Response Patterns to Treatment in Glioblastoma (GBM) Oncology Patients Based on Host Response Evaluation During Anti-cancer Treatments
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Glioblastoma
Lead sponsor: OncoHost Ltd.
Sponsor class: INDUSTRY
First posted: 2020-01-07
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients recruited for the study except for

1. Patients who discontinued the TMZ during the first 2 weeks of treatment, unless the drug was stopped due to tumor progression.
2. Patients who didn't receive at least 46 Gy in the 6 weeks regimen or 30 Gy in the 3 weeks regimen, unless the treatment was stopped due to grade 3 and higher toxicity.
3. Patients who chose to discontinue the treatment for reasons other than disease progression or serious side effects unless the treatment was stopped due to grade 3 and highertoxicity.

Brief summary: PROPHETIC GBM - Predicting response patterns to treatment in Glioblastoma (GBM) oncology patients based on host response evaluation during anti-cancer treatments

Detailed description: The goal of this research study is identify new host response proteins, pathways and mechanisms that are associated with responsiveness to GBM treatment modalities.

This will serve as a tool for physicians when making treatment decisions. The investigators also aim to identify the metabolic pathways that could lead to better therapeutic options. The patients will be given their treatment according to the institute's standard of care. The patients will provide up to 5 blood samples and clinical data will be collected from their medical records.

The data obtained from the blood samples and the medical records of the patients will be used to search for potential mechanisms that are involved in response to treatment, and to identify potential targets to increase the response, and hence, increase treatment effectiveness or suggest potential new treatments.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study-specific procedures.
2. Male or female aged at least 18 years.
3. KPS not less than 50.
4. Normal hematologic, renal and liver function:

   1. Absolute neutrophil count above 1500/mm3, platelets above 100,000/mm3, hemoglobin above 9 g/dL;
   2. Creatinine concentration not more than 1.4 mg/dL, or creatinine clearance above 40 mL/min;
   3. Total bilirubin below 1.5 mg/dL, ALT+ AST levels not more than 3 times above the upper normal limit.
5. Patients planned to receive standard of care TMZ+RT treatment; TTF therapy during RT is permitted.

Exclusion Criteria:

1. Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of surgery. Except for basal cell carcinomas and squamous cell carcinomas that have been completely excised and considered cured at least 12 months prior to screening, and carcinoma in situ of the cervix that have been completely excised and cured at least 5 years prior to screening.
2. Participation in another clinical trial which includes an investigational drug.
3. Generalized impairment or mental incompetence that would render the patient unable to understand his/her participation in the study.
4. Pregnancy.

Primary outcomes:
measure: Response to treatment
timeFrame: One month after completion of TMZ + RT
measure: Response to treatment
timeFrame: 3 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 6 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 9 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 12 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 18 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 24 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 30 months after treatment completion in the first year
measure: Response to treatment
timeFrame: 36 months after treatment completion in the first year
measure: Blood levels of proteins
timeFrame: Pre-chemoradiation therapy - 7 days or less before the first administration
measure: Blood levels of proteins
timeFrame: After the first chemoradiation administration - at least 24 h after the first temozolomide (TMZ) dose, and between 24-48 h after the first radiation therapy (RT) dose
measure: Blood levels of proteins
timeFrame: 21+/-2 days after the first TMZ dose
measure: Blood levels of proteins
timeFrame: At first detection of progressive disease (PD) based on MRI evaluation during follow-up assessed up to 36 months
measure: Blood levels of proteins
timeFrame: If the previous detection of progression turned out to be pseudo-progression, then an additional blood sample should be drawn at time of progression, assessed up to 36 months
Secondary outcomes:
measure: OS
timeFrame: Until death or 3 years
measure: PFS
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam medical center
city: Petah tikva
country: Israel
facility: Rabin medical center
city: Tel Aviv
country: Israel
facility: Sourasky medical center
city: Tel HaShomer
country: Israel
facility: Sheba medical center
Study officials:
affiliation: Sourasky Medical Center
name: Dror Limon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shaked Y. Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects. Nat Rev Clin Oncol. 2016 Oct;13(10):611-26. doi: 10.1038/nrclinonc.2016.57. Epub 2016 Apr 26.
citation: Shaked Y, Kerbel RS. Antiangiogenic strategies on defense: on the possibility of blocking rebounds by the tumor vasculature after chemotherapy. Cancer Res. 2007 Aug 1;67(15):7055-8. doi: 10.1158/0008-5472.CAN-07-0905.
citation: Shaked Y, Bocci G, Munoz R, Man S, Ebos JM, Hicklin DJ, Bertolini F, D'Amato R, Kerbel RS. Cellular and molecular surrogate markers to monitor targeted and non-targeted antiangiogenic drug activity and determine optimal biologic dose. Curr Cancer Drug Targets. 2005 Nov;5(7):551-9. doi: 10.2174/156800905774574020.