GliosarcomaEarly Phase 1NCT03020017
NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery
A Early Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Targeted Molecular Therapy in people with Gliosarcoma and Recurrent Glioblastoma, run by Northwestern University at 1 site in United States.
Trial summary
The purpose of this research study is to evaluate the safety of the study drug, NU-0129, based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the surface of a small spherical gold nanoparticle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gliosarcoma, Recurrent Glioblastoma
- What is being tested?
- Laboratory Biomarker Analysis, Pharmacological Study and Targeted Molecular Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 25 May 2017to 19 Aug 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma (GS)
- Patients must have measurable disease by Response Assessment in Neuro-Oncology (RANO) 2010 criteria at the time of registration (pre-operative)
- Patients must have failed at least one regimen of chemo or radiation therapy; NOTE: There is no limit to the number or types of prior therapy
- The patient must be a candidate for surgical debulking (either subtotal or gross total resection); biopsy-only candidates will not be eligible
- All patients must be capable to voluntarily sign an informed consent indicating that they are aware of the investigational nature of this study prior to registration
- Patients must have a Karnofsky performance status of >= 70
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- Patients must have adequate bone marrow, liver, coagulation and renal function within 7days prior to study registration, as defined below:
- White blood cell count (WBC) >= 3,000/uL
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count of >= 100,000/mm^3 (Note: Transfusion or growth factor may be used for eligibility outside of 7 days)
- Hemoglobin >= 8 mg/dL (Note: Transfusion may be used for eligibility outside of 7 days)
- Bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 x ULN
- Creatinine =< 1.5 x ULN
- Urine protein =< 3 x ULN
- Cholesterol =< 300 mg/dL
- International normalized ration (INR) =< 1.5 x ULN
- Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x ULN
- Any patient who has had a recent surgery should have recovered from all effects of the surgery and be cleared by their surgeon
- Patients must have confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications (10 unstained slides) prior to study enrollment
- Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 28 days following completion of therapy; should a female patient, or a male patient's partner, become pregnant or suspect she is pregnant while participating in this study, the patient should inform her or his treating physician immediately
- NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
- FOCBP must have a negative pregnancy test (either urine or serum) within 14 days prior to registration
Who cannot join
- Patients must not have any significant infections or medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate NU-0129
- Patients must not have a history of any other cancer unless they are in complete remission and off of all therapy for that disease for a minimum of 3 years
- Note: Non-melanoma skin cancer or carcinoma in-situ of the cervix are exceptions and may be permitted after discussion with study quality assurance manager (QAM)
- Patients must not have had radiation therapy within 12 weeks prior to registration
- Patients must not have had prior cancer therapy (including biologic, cytotoxic, and experimental therapies, nitrosoureas, and Gliadel wafers or other surgically implantable antitumor treatment) within 21 days of registration; if questions arise, please ask the principal investigator (PI)
- NOTE: Patients must not have Novocure within 24 hours
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- Hormonal tumor therapies should not be administered within 14 days of registration; exceptions may be discussed with the PI
- Patients must not have symptomatic hypertension
- Patients with known human immunodeficiency virus (HIV) infection or chronic or acute hepatitis B or C are not eligible; Note: Patients do not need to have HIV, hepatitis B, or hepatitis C testing at screening
- Female patients who are pregnant or breast feeding are not eligible
- Patients are not eligible if they are unwilling or unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 0 First-In-Human Study Using NU-0129: A Spherical Nucleic Acid (SNA) Gold Nanoparticle Targeting BCL2L12 in Recurrent Glioblastoma Multiforme or Gliosarcoma Patients
The purpose of this research study is to evaluate the safety of the study drug, NU-0129, based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that carry blood to the brain). Once within the tumor, the nucleic acid component is able to target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of programmed cell death, thus promoting tumor growth. Researchers think that targeting the Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma multiforme (GBM) or gliosarcoma (GS).
SECONDARY OBJECTIVES:
- To analyze drug concentration in serum at specific time points after drug administration.
II. To demonstrate intratumoral penetration of NU-0129. III. To assess the feasibility of giving NU-0129 as a standard treatment for recurrent GBM or GS.
TERTIARY OBJECTIVES:
- To analyze tumor tissue for Bcl2L12 expression levels after NU-0129 administration.
II. Preliminary response (progression free survival [PFS] and overall survival [OS] at 6 months; overall response rate [ORR]).
OUTLINE:
Patients receive NU-0129 intravenously (IV) over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.
After completion of study treatment, patients are followed up at 7, 14, 21, and 28 days and then every 84 days for up to 2 years.
- Conditions
- Gliosarcoma, Recurrent Glioblastoma
- Being tested
- Laboratory Biomarker Analysis, Pharmacological Study, Targeted Molecular Therapy
- Medical subject headings
- Gliosarcoma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
Targeted Molecular TherapyDrug
Also called molecularly targeted therapy
Given NU-0129 IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (NU-0129) | Experimental | Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Targeted Molecular Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Adverse Events
To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal
Measured: Up to 21 days after study drug administration
Secondary outcomes (4)
NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration
Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
Measured: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
Biodistribution of NU-0129 in Tumor Tissue
Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H\&E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.
Measured: At time of surgery
Feasibility of Giving NU-0129 as a Standard Treatment
Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.
Measured: At time of infusion (8-48 hours prior to resection) and during surgery
NU-0129 Concentration in Blood After Drug Administration Using Half-life
Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
Measured: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study start25 May 2017
- Primary completion6 Sep 2018
- Study completion19 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GliosarcomaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Priya Kumthekar, Northwestern University
- Investigators
- Priya Kumthekar, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03020017
- Sponsor's protocol ID
- NU 16C01
- Other IDs
- STU00203790, NU 16C01, P30CA060553, NCI-2016-02007
- Status last verified
- Aug 2022
- First submitted
- 11 Jan 2017
- Last updated
- 26 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0 First-In-Human Study Using NU-0129: A Spherical Nucleic Acid (SNA) Gold Nanoparticle Targeting BCL2L12 in Recurrent Glioblastoma Multiforme or Gliosarcoma Patients
- ClinicalTrials.gov ID
- NCT03020017
- Acronym / sponsor ID
- NU 16C01
- Conditions
- Gliosarcoma, Recurrent Glioblastoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 May 2017 (actual)
- Primary completion
- 6 Sep 2018 (actual)
- Study completion
- 19 Aug 2020 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Posted 26 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to evaluate the safety of the study drug, NU-0129, based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that carry blood to the brain). Once within the tumor, the nucleic acid component is able to target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of programmed cell death, thus promoting tumor growth. Researchers think that targeting the Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma multiforme (GBM) or gliosarcoma (GS).
SECONDARY OBJECTIVES:
- To analyze drug concentration in serum at specific time points after drug administration.
II. To demonstrate intratumoral penetration of NU-0129. III. To assess the feasibility of giving NU-0129 as a standard treatment for recurrent GBM or GS.
TERTIARY OBJECTIVES:
- To analyze tumor tissue for Bcl2L12 expression levels after NU-0129 administration.
II. Preliminary response (progression free survival [PFS] and overall survival [OS] at 6 months; overall response rate [ORR]).
OUTLINE:
Patients receive NU-0129 intravenously (IV) over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.
After completion of study treatment, patients are followed up at 7, 14, 21, and 28 days and then every 84 days for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (NU-0129) | Experimental | Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Drug: Targeted Molecular TherapyPatients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma (GS)
- Patients must have measurable disease by Response Assessment in Neuro-Oncology (RANO) 2010 criteria at the time of registration (pre-operative)
- Patients must have failed at least one regimen of chemo or radiation therapy; NOTE: There is no limit to the number or types of prior therapy
- The patient must be a candidate for surgical debulking (either subtotal or gross total resection); biopsy-only candidates will not be eligible
- All patients must be capable to voluntarily sign an informed consent indicating that they are aware of the investigational nature of this study prior to registration
Key exclusion criteria (11 listed)
- Patients must not have any significant infections or medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate NU-0129
- Patients must not have a history of any other cancer unless they are in complete remission and off of all therapy for that disease for a minimum of 3 years
- Patients must not have had radiation therapy within 12 weeks prior to registration
- Patients must not have had prior cancer therapy (including biologic, cytotoxic, and experimental therapies, nitrosoureas, and Gliadel wafers or other surgically implantable antitumor treatment) within 21 days of registration; if questions arise, please ask the principal investigator (PI)
- Hormonal tumor therapies should not be administered within 14 days of registration; exceptions may be discussed with the PI
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (NU-0129) |
| Pharmacological StudyCorrelative studies | Other | Treatment (NU-0129) |
| Targeted Molecular TherapyAlso: molecularly targeted therapyGiven NU-0129 IV | Drug | Treatment (NU-0129) |
Primary outcome
Number of Patients With Adverse Events
Time frame: Up to 21 days after study drug administration
To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal
4 secondary outcomes
NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration
Time frame: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
Biodistribution of NU-0129 in Tumor Tissue
Time frame: At time of surgery
Feasibility of Giving NU-0129 as a Standard Treatment
Time frame: At time of infusion (8-48 hours prior to resection) and during surgery
NU-0129 Concentration in Blood After Drug Administration Using Half-life
Time frame: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Priya Kumthekar, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Targeted Molecular Therapy in people with Gliosarcoma and Recurrent Glioblastoma, run by Northwestern University 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 25 inclusion and 11 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 26 Aug 2022. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Adverse Events (time frame: Up to 21 days after study drug administration). 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 26 Aug 2022.