Cancer Stem Cell High-Throughput Drug Screening Study

NCT02654964 | Completed Phase 1 DMC

• 1 other identifier: HTS Drug Screening Study
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

A study to determine the safety of CSC/ HTS-based combination drug therapy in subjects who have GBM that has recurred or progressed following prior radiation therapy and TMZ.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (4)

• Tumor size

  1 year

• Progression free survival

  1 year

• Overall response rate

  1 year

• Overall survival

  1 year

Study Arms (1)

Treatment Arm

EXPERIMENTAL

A Drug Combination Treatment will be determined through High Throughput Screening. The classes of drugs this combination therapy will be comprised from are: Antineoplastic Anti-infective Antiemetic Antihyperlipidemic Anti-inflammatory Antihistamine Antihypertensive Antidepressant Cardiotonic Alcohol antagonist Diuretic Antipsychotic NMDA receptor antagonist Antidiabetic Immunosuppressant Anticonvulsant Antimethemoglobinemic Sclerosing agent

Drug: Combination Drug Therapy

Interventions

Combination Drug Therapy DRUG

Up to 3 of 73 possible interventions from the drug classes listed below will be selected based on their potency against CSCs, potential for synergy without cross-reactive toxicities, drug safety profiles, pharmacokinetics, and drug-drug interactions. Those patients that have GBM that has recurred (as defined by RANO (45)), and for whom HTS was successfully completed, will be eligible to continue to the treatment component of the study to receive the drug cocktail comprised from the following drug classes: Antineoplastic Anti-infective Antiemetic Antihyperlipidemic Anti-inflammatory Antihistamine Antihypertensive Antidepressant Cardiotonic Alcohol antagonist Diuretic Antipsychotic NMDA receptor antagonist Antidiabetic Immunosuppressant Anticonvulsant Antimethemoglobinemic Sclerosing agent

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Determined at pre-screening:
• A histological diagnosis of GBM \[WHO grade IV\].
• Subjects ≥18 years of age
• Signed informed consent for tumor collection prior to initiation of any study-specific procedure. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment
• Patients must have a life expectancy of \>12 weeks
• Determined at or around surgery, and prior to performing HTS:
• Patients must have a surgically accessible tumor with the intent for a gross or near total resection of the tumor mass (GBM, WHO grade IV)
• Collection of sufficient tumor material for processing CSCs
• Determined at or around tumor recurrence, and after completion of HTS:
• Disease progression following radiation and TMZ therapy (as defined by RANO criteria (45); Appendix 3). Unlimited relapses are allowed, provided the functional status and other eligibility criteria for enrollment are met
• Determined at baseline:
• Signed informed consent for CSC/HTS based therapy prior to initiation of any study-specific procedure or treatment. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment
• Patients must have a KPS rating of ≥70 (see Appendix 4: Karnofsky Performance Scale)
• Patients must have recovered from the toxic effects of prior therapy to \< Grade 2 toxicity per NCI CTCAE version 4 (Appendix 6) prior to Day 1 of Cycle 1. The minimum duration required between prior therapy and initiation of study drug treatment is as follows:
• At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence (such as histological confirmation) in which case at least 4 weeks from completion of radiation will suffice

You may not qualify if:

• Any condition, including the presence of clinically significant laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
• Active infection, (including known Acquired Immunodeficiency Syndrome (AIDS) and Hepatitis C) within 3 days prior to the study enrollment
• Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
• Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent unless they have a legal authorized representative that can consent on their behalf
• Inadequately controlled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months
• History of stroke or transient ischemic attack within 6 months
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
• History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• Grade 2 or higher peripheral neuropathy per NCI CTCAE version 4
• History of abdominal fistula or gastrointestinal (GI) perforation within 6 months.

Sponsors & Collaborators

• Swedish Medical Center: lead

Study Sites (1)

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Drug Therapy, Combination

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Charles Cobbs, MD

  Swedish Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: January 13, 2016
• Study Start: December 1, 2015
• Primary Completion: November 1, 2021
• Study Completion: June 1, 2023
• Last Updated: April 10, 2024

Record last verified: 2024-04

Locations

US (1)