Predicting Response Patterns to Treatment in Glioblastoma (GBM) Patients (PROPHETIC)

Predicting Response Patterns to Treatment in Glioblastoma (GBM) Oncology Patients Based on Host Response Evaluation During Anti-cancer Treatments

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

Study Overview

• Status: Suspended
• Conditions: Glioblastoma

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.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center
  • Petah tikva, Israel
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Sourasky Medical Center
  • Tel HaShomer, Israel
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
GBM patients; Newly diagnosed patients above 18 years of age with GBM receiving standard of care, i.e., maximal surgical resection possible followed by radiation therapy (RT) plus temozolomide (TMZ) therapy and maintenance TMZ.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment	complete remission (CR); partial remission (PR), stable disease (SD), progressive disease (PD), suspected pseudo-progression, as defined by RANO	One month after completion of TMZ + RT
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	3 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	6 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	9 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	12 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	18 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	24 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	30 months after treatment completion in the first year
Response to treatment	CR, PR, SD, PD, suspected pseudo-progression, as defined by RANO	36 months after treatment completion in the first year
Blood levels of proteins	Blood levels of proteins representing the Host response at baseline	Pre-chemoradiation therapy - 7 days or less before the first administration
Blood levels of proteins	Changes in Blood levels of proteins representing the Host response compared to baseline	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
Blood levels of proteins	Changes in Blood levels of proteins representing the Host response compared to baseline	21+/-2 days after the first TMZ dose
Blood levels of proteins	Changes in Blood levels of proteins representing the Host response compared to baseline	At first detection of progressive disease (PD) based on MRI evaluation during follow-up assessed up to 36 months
Blood levels of proteins	Changes in Blood levels of proteins representing the Host response compared to baseline	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	Until death or 3 years
PFS	Progression free survival	up to 3 years

Collaborators and Investigators

• Sponsor: OncoHost Ltd.
• Investigators: Principal Investigator: Dror Limon, MD, Sourasky Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: OH-GBMHR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No