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NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

Primary Purpose

Gliosarcoma, Recurrent Glioblastoma

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Laboratory Biomarker Analysis

Pharmacological Study

Targeted Molecular Therapy

About this trial

This is an interventional treatment trial for Gliosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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

Exclusion Criteria:

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
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

Sites / Locations

Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (NU-0129)

Arm Description

Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

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.

NU-0129 Concentration in Blood After Drug Administration Using Half-life

Full Information

NCT ID

NCT03020017

First Posted

January 11, 2017

Last Updated

August 5, 2022

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03020017

Brief Title

NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

May 25, 2017 (Actual)

Primary Completion Date

September 6, 2018 (Actual)

Study Completion Date

August 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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: I. To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma multiforme (GBM) or gliosarcoma (GS). SECONDARY OBJECTIVES: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gliosarcoma, Recurrent Glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (NU-0129)

Arm Type

Experimental

Arm Description

Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

Pharmacological Study

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Targeted Molecular Therapy

Other Intervention Name(s)

molecularly targeted therapy

Intervention Description

Given NU-0129 IV

Primary Outcome Measure Information:

Title

Number of Patients With Adverse Events

Description

Time Frame

Up to 21 days after study drug administration

Secondary Outcome Measure Information:

Title

NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration

Description

Time Frame

At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion

Title

Biodistribution of NU-0129 in Tumor Tissue

Description

Time Frame

At time of surgery

Title

Feasibility of Giving NU-0129 as a Standard Treatment

Description

Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.

Time Frame

At time of infusion (8-48 hours prior to resection) and during surgery

Title

NU-0129 Concentration in Blood After Drug Administration Using Half-life

Description

Time Frame

At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Priya Kumthekar, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

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NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

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