Glioblastoma MultiformePhase 1NCT02654964
Cancer Stem Cell High-Throughput Drug Screening Study
A Phase 1 study testing Combination Drug Therapy in people with Glioblastoma Multiforme, run by Swedish Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Combination Drug Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- 4 weeks from prior cytotoxic chemotherapy
- 4 weeks from prior experimental drug
- 6 weeks from nitrosoureas
- 3 weeks from procarbazine
- 1 week for non-cytotoxic agents.
- Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria:
- Hemoglobin (Hgb)> 8 g/dL
- Absolute Neutrophil Count (ANC) > 1,000/mm3
- Platelet count > 100,000/mm3
- Creatinine < 2 mg/dL
- Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal (ULN)
- Patients of childbearing potential must agree to use an adequate method of contraception for the duration of the study, and for 90 days following discontinuation of study drugs
- Females of childbearing potential must have a negative pregnancy test
- Patients must be negative for HIV, Hepatitis B and C
- Patients are cooperative and able to complete all the assessment procedures.
Who cannot join
- 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)
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- 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.
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Allergies to reagents used in this study
- Women of child bearing age not willing to use a reliable form of contraception
- Pregnancy (positive pregnancy test) or lactation
- Patient is positive for HIV, Hepatitis B or C
- Concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) Patients must discontinue an EIAED at least two weeks prior to starting study drug
- Concurrent use of herbal medications
- Patient is simultaneously participating in another clinical trial during the Phase 1 (treatment phase) of this study. Patients may enroll/consent in the Phase 0 portion of this study for tissue collection and HTS while being treated with standard of care or clinical trial for newly diagnosed GBM prior to recurrence. Inability or unwilling to comply with protocol or study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 0/1 Study of Combination Drug Therapy For Glioblastoma Based on Personalized Cancer Stem Cell (CSC) High-Throughput Drug Screening (HTS)
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.
Read the detailed description
This protocol describes a prospective single-center Phase 0/1 open-label study to evaluate the safety and efficacy of a high-throughput drug sensitivity assay to predict targeted therapies for patients who have GBM that has recurred or progressed following prior radiation therapy and TMZ. The underlying hypothesis is that treatment of patients with up to 3 lead candidates identified from individualized CSC/ HTS assays will safely (1) delay disease progression, and (2) increase survival. There is an abundance of literature strongly supporting the importance of a regimen for targeting CSCs and preventing tumor recurrence, as an additional strategy to improve the overall prognosis of cancer patients.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Combination Drug Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination Drug TherapyDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Combination Drug Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor size
Measured: 1 year
Progression free survival
Measured: 1 year
Overall response rate
Measured: 1 year
Overall survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study startDec 2015
- Primary completionNov 2021
- Study completionJun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charles Cobbs, MD, Principal investigator, Swedish Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654964
- Sponsor's protocol ID
- HTS Drug Screening Study
- Status last verified
- Apr 2024
- First submitted
- 19 Nov 2015
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0/1 Study of Combination Drug Therapy For Glioblastoma Based on Personalized Cancer Stem Cell (CSC) High-Throughput Drug Screening (HTS)
- ClinicalTrials.gov ID
- NCT02654964
- Acronym / sponsor ID
- HTS Drug Screening Study
- Conditions
- Glioblastoma Multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Swedish Medical CenterUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Nov 2021 (actual)
- Study completion
- Jun 2023 (actual)
- First posted
- 13 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This protocol describes a prospective single-center Phase 0/1 open-label study to evaluate the safety and efficacy of a high-throughput drug sensitivity assay to predict targeted therapies for patients who have GBM that has recurred or progressed following prior radiation therapy and TMZ. The underlying hypothesis is that treatment of patients with up to 3 lead candidates identified from individualized CSC/ HTS assays will safely (1) delay disease progression, and (2) increase survival. There is an abundance of literature strongly supporting the importance of a regimen for targeting CSCs and preventing tumor recurrence, as an additional strategy to improve the overall prognosis of cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Combination Drug TherapyA 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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
- 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)
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination Drug TherapyUp 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 | Drug | Treatment Arm |
Primary outcome
Tumor size
Time frame: 1 year
Progression free survival
Time frame: 1 year
Overall response rate
Time frame: 1 year
Overall survival
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Cobbs, MD principal investigator
Swedish Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Combination Drug Therapy in people with Glioblastoma Multiforme, run by Swedish Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor size (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024; AzTrials last refreshed its copy on 1 Nov 2026.