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Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma

Primary Purpose

Locally Advanced Unresectable Primary Central Chondrosarcoma, Metastatic Primary Central Chondrosarcoma, Unresectable Primary Central Chondrosarcoma

Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belinostat
Biopsy
Biospecimen Collection
Computed Tomography
Decitabine and Cedazuridine
Guadecitabine
Magnetic Resonance Imaging
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Unresectable Primary Central Chondrosarcoma

Eligibility Criteria

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

Inclusion Criteria:

  • Patients must have biopsy-proven conventional chondrosarcoma (CS) which is:

    • Either metastatic or locally advanced and unresectable, and
    • Measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, and
    • Amenable to biopsy with imaging guidance at no or acceptable risk to the patient as defined by institutional guidelines for research-related biopsies or the treating investigator's assessment
    • In addition, the following criteria must be met:

      • Patients must have at least one lesion measurable by RECIST version 1.1 criteria which has not been previously irradiated
      • Patients who have histologic evidence of grade 1 chondrosarcoma only must either be symptomatic from their disease in the opinion of the treating investigator or demonstrate radiographic evidence of disease progression in the 3 months prior to initiation of study treatment
    • Note: Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study
  • Patients may have been treated with any number of prior systemic therapies. Because there are no Food and Drug Administration (FDA)-approved treatments for this disease, patients who have received no prior systemic therapy are also eligible. However, disease must be deemed surgically unresectable
  • Age >= 18 years. Chondrosarcoma is rarely encountered in children and adolescents
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,000/mm^3
  • Hemoglobin 8 g/dL
  • Platelet count >= 75,000/mm^3
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional ULN
  • Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 45 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, if patients have been clinically asymptomatic, and if patients have not received systemic corticosteroids for at least 28 days. Patients with brain metastases not meeting these criteria are not eligible
  • Patients must be disease-free of prior invasive malignancies for > 5 years, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

    • NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • The effects of belinostat and SGI-110 (guadecitabine) or ASTX727 on the developing human fetus are unknown. For this reason, and because the DNA methyltransferase inhibitor decitabine, the active metabolite of SGI-110 (guadecitabine) and a component of ASTX727, is known to be teratogenic, and because belinostat may cause teratogenicity and/or embryo-fetal lethality by virtue of targeting actively dividing cells, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 6 months after the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of belinostat and SGI-110 (guadecitabine) or ASTX727 administration
  • Patients must be able to understand and willing to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

  • Patients with dedifferentiated, mesenchymal, or clear cell chondrosarcoma are not eligible
  • Patients who have not recovered from adverse events (AEs) (i.e., have residual toxicities > grade 1) due to prior anti-cancer therapy are not allowed, with the exceptions of alopecia and endocrinopathies from prior immunotherapy-based treatments that are well-controlled with hormone replacement. In addition, the following time periods must elapse between the last dose of prior anti-cancer treatment and initiation of study treatment on this protocol:

    • Cytotoxic chemotherapy or biologic, including immunotherapy: 28 days
    • Small molecule targeted drug: 21 days or 5 half-lives, whichever is shorter. If 5 half-lives is shorter than 21 days, then 21 days applies.
    • Radiation: 28 days, except for palliative radiation, for which 14 days applies
  • Patients who are receiving any other investigational agents
  • Patients with known history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to SGI-110 (guadecitabine), its active metabolite decitabine, or ASTX727, or belinostat
  • Chronic use of any medications or substances that are strong inhibitors of UGT1A1 is not allowed. Patients must switch to alternative medications 7-14 days before treatment with belinostat. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients with any known UGT1A1 polymorphism, heterozygous or homozygous, associated with reduced function (UGT1A1*6, UGT1A1*28, or UGT1A1*60)
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because SGI-110 (guadecitabine) is a derivative of decitabine, and ASTX727 contains the agent decitabine, which has the potential for teratogenic or abortifacient effects, and because belinostat may cause teratogenicity and/or embryo-fetal lethality by virtue of targeting actively dividing cells. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with SGI-110 (guadecitabine), ASTX727 and belinostat, breastfeeding should be discontinued
  • Prolongation of the heart-rate corrected QT (QTc) interval >= 450 ms (i.e., grade 1 or higher) on the screening electrocardiogram (ECG) prior to initiation of study treatment. If baseline QTc on screening ECG is >= 450 ms (i.e., grade 1 or higher):

    • Check potassium and magnesium serum levels, and
    • Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm a QTc interval < 450 ms

Sites / Locations

  • Mayo Clinic Hospital in Arizona
  • City of Hope Comprehensive Cancer Center
  • Los Angeles County-USC Medical Center
  • USC / Norris Comprehensive Cancer Center
  • USC Norris Oncology/Hematology-Newport Beach
  • UCHealth University of Colorado Hospital
  • Yale University
  • UM Sylvester Comprehensive Cancer Center at Coral Gables
  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
  • Mayo Clinic in Florida
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • UM Sylvester Comprehensive Cancer Center at Plantation
  • Moffitt Cancer Center
  • Northwestern University
  • HaysMed University of Kansas Health System
  • University of Kansas Cancer Center
  • Lawrence Memorial Hospital
  • University of Kansas Cancer Center-Overland Park
  • Ascension Via Christi - Pittsburg
  • Salina Regional Health Center
  • University of Kansas Health System Saint Francis Campus
  • University of Kansas Hospital-Westwood Cancer Center
  • Mayo Clinic in Rochester
  • Siteman Cancer Center at West County Hospital
  • Truman Medical Centers
  • University of Kansas Cancer Center - North
  • University of Kansas Cancer Center - Lee's Summit
  • University of Kansas Cancer Center at North Kansas City Hospital
  • Washington University School of Medicine
  • Siteman Cancer Center-South County
  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • Ohio State University Comprehensive Cancer Center
  • University of Oklahoma Health Sciences Center
  • Thomas Jefferson University Hospital
  • University of Pittsburgh Cancer Institute (UPCI)
  • M D Anderson Cancer Center
  • Huntsman Cancer Institute/University of Utah
  • Virginia Commonwealth University/Massey Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (belinostat, guadecitabine, ASTX727)

Arm Description

Patients receive guadecitabine SC or ASTX727 PO on days 1-5. Patients also receive belinostat IV over 30 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood during screening, tumor biopsy during screening and on study, and MRI or CT throughout the trial.

Outcomes

Primary Outcome Measures

Objective response rate

Secondary Outcome Measures

Presence of treatment related adverse events (AEs)
Adverse events will be recorded at each clinical visit and will be categorized according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The attribution of AEs to each of the study drugs will also be recorded. Adverse event rates that are possibly, probably, or definitely related to treatment will be reported as counts and percentages per AE by grade and the number of patients with a given maximal grade of toxicity. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.
Occurrence of dose limiting toxicity (DLT)
DLTs are defined as the following toxicities which are attributed to the study drug(s) and not to disease, and which occur (or first become evident) during a prespecified timeframe. Will also report the frequency and percentage of DLTs. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.
Progression free survival (PFS)
The Kaplan-Meier method will be used to evaluate time to event endpoints. Median PFS will be reported with a 95% confidence interval. Data will be presented as Kaplan Meier plots. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.

Full Information

First Posted
April 9, 2020
Last Updated
September 26, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04340843
Brief Title
Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma
Official Title
A Phase 2 Study of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Suspended
Why Stopped
Other - Completed stage 1 accrual
Study Start Date
September 8, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies the effect of belinostat and SGI-110 (guadecitabine) or ASTX727 in treating patients with conventional chondrosarcoma that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to other places in the body (metastatic). Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as guadecitabine and ASTX727, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving belinostat in combination with guadecitabine or ASTX727 may lower the chance of unresectable and metastatic chondrosarcoma growing or spreading.
Detailed Description
PRIMARY OBJECTIVE: I. To conduct a phase 2 clinical trial to evaluate whether combination treatment with belinostat and decitabine and cedazuridine (ASTX727) shows preliminary evidence of clinical activity in unresectable or metastatic conventional chondrosarcoma (CS) using an objective response rate endpoint. SECONDARY OBJECTIVES: I. To evaluate the toxicity profile associated with the belinostat and ASTX727. II. To evaluate the progression free survival (PFS) associated with the belinostat and ASTX727. III. To evaluate the toxicity profile, objective response rate and progression free survival among the initial six patients treated with belinostat and SGI-110 (guadecitabine) prior to Amendment 5 in which ASTX727 was substituted for SGI-110 (guadecitabine). CORRELATIVE OBJECTIVES: I. To determine the IDH1/2 mutational status of subject's tumors and to evaluate for a relationship between presence of IDH1/2 mutation and clinical benefit from study treatment. II. To conduct ribonucleic acid sequencing (RNAseq) analysis using baseline and on-treatment tissue biopsies to study the effects of study treatment on CS gene expression patterns and identify candidate genes which may underlie treatment efficacy. III. To evaluate for changes in global deoxyribonucleic acid (DNA) methylation levels using baseline and on-treatment biopsies and correlate changes in global methylation with clinical benefit from study treatment. IV. To use multiplex immunohistochemistry to interrogate the immune microenvironment in baseline and on-treatment tissue biopsies to define changes in infiltrating immune cell subsets and PD-L1/major histocompatibility complex (MHC) expression by immune and tumor cells associated with study treatment. OUTLINE: Patients receive guadecitabine subcutaneously (SC) or ASTX727 orally (PO) on days 1-5. Patients also receive belinostat intravenously (IV) over 30 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood during screening, tumor biopsy during screening and on study, and magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. After completion of study treatment, patients are followed up every 3 months for 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Unresectable Primary Central Chondrosarcoma, Metastatic Primary Central Chondrosarcoma, Unresectable Primary Central Chondrosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (belinostat, guadecitabine, ASTX727)
Arm Type
Experimental
Arm Description
Patients receive guadecitabine SC or ASTX727 PO on days 1-5. Patients also receive belinostat IV over 30 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood during screening, tumor biopsy during screening and on study, and MRI or CT throughout the trial.
Intervention Type
Drug
Intervention Name(s)
Belinostat
Other Intervention Name(s)
Beleodaq, PXD 101, PXD101
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Drug
Intervention Name(s)
Decitabine and Cedazuridine
Other Intervention Name(s)
ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inqovi
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Guadecitabine
Other Intervention Name(s)
DNMT inhibitor SGI-110, S110, SGI-110
Intervention Description
Given SC
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Primary Outcome Measure Information:
Title
Objective response rate
Time Frame
Within 6 months after initiating study treatment
Secondary Outcome Measure Information:
Title
Presence of treatment related adverse events (AEs)
Description
Adverse events will be recorded at each clinical visit and will be categorized according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The attribution of AEs to each of the study drugs will also be recorded. Adverse event rates that are possibly, probably, or definitely related to treatment will be reported as counts and percentages per AE by grade and the number of patients with a given maximal grade of toxicity. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.
Time Frame
Up to 24 months post treatment
Title
Occurrence of dose limiting toxicity (DLT)
Description
DLTs are defined as the following toxicities which are attributed to the study drug(s) and not to disease, and which occur (or first become evident) during a prespecified timeframe. Will also report the frequency and percentage of DLTs. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.
Time Frame
During the first cycle (28 days)
Title
Progression free survival (PFS)
Description
The Kaplan-Meier method will be used to evaluate time to event endpoints. Median PFS will be reported with a 95% confidence interval. Data will be presented as Kaplan Meier plots. Will be reported separately for the population of patients receiving belinostat and SGI-110 (guadecitabine) and the population of patients receiving belinostat and ASTX727.
Time Frame
Time from first treatment with the study drug to the earliest of either disease progression or death from any cause, assessed up to 24 months
Other Pre-specified Outcome Measures:
Title
IDH1/2 mutational status
Description
Will compare the difference in the objective response rate among patients with IDH1/2 mutations as compared those without IDH1/2 mutations using Fisher's exact test.
Time Frame
Up to 24 months post treatment
Title
Changes in expression of conventional chondrosarcoma genes
Description
Data from ribonucleic acid sequencing will be analyzed. Differential expression profiles between baseline and on-treatment samples will be analyzed at the gene level and gene expression changes defined as significant based on absolute log2 fold changes > 2 and adjusted p values < 0.005 for each comparison with consideration of the false discovery rate.
Time Frame
Baseline up to 24 months post treatment
Title
Changes in global deoxyribonucleic acid methylation
Description
A Wilcoxon signed-rank test with continuity correction will be used to calculate P values for comparing methylation level distribution at the different time points.
Time Frame
Baseline up to 24 months post treatment
Title
Changes in tumor microenvironment
Description
For quantitative immune multiplexing, data is derived from inForm software, and changes in defined immune cell subsets and expression between baseline and on-treatment samples will be assessed using paired T-tests.
Time Frame
Baseline up to 24 months post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have biopsy-proven conventional chondrosarcoma (CS) which is: Either metastatic or locally advanced and unresectable, and Measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, and Amenable to biopsy with imaging guidance at no or acceptable risk to the patient as defined by institutional guidelines for research-related biopsies or the treating investigator's assessment In addition, the following criteria must be met: Patients must have at least one lesion measurable by RECIST version 1.1 criteria which has not been previously irradiated Patients who have histologic evidence of grade 1 chondrosarcoma only must either be symptomatic from their disease in the opinion of the treating investigator or demonstrate radiographic evidence of disease progression in the 3 months prior to initiation of study treatment Note: Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study Patients may have been treated with any number of prior systemic therapies. Because there are no Food and Drug Administration (FDA)-approved treatments for this disease, patients who have received no prior systemic therapy are also eligible. However, disease must be deemed surgically unresectable Age >= 18 years. Chondrosarcoma is rarely encountered in children and adolescents Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Absolute neutrophil count >= 1,000/mm^3 Hemoglobin 8 g/dL Platelet count >= 75,000/mm^3 Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional ULN Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 45 mL/min/1.73 m^2 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, if patients have been clinically asymptomatic, and if patients have not received systemic corticosteroids for at least 28 days. Patients with brain metastases not meeting these criteria are not eligible Patients must be disease-free of prior invasive malignancies for > 5 years, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better The effects of belinostat and SGI-110 (guadecitabine) or ASTX727 on the developing human fetus are unknown. For this reason, and because the DNA methyltransferase inhibitor decitabine, the active metabolite of SGI-110 (guadecitabine) and a component of ASTX727, is known to be teratogenic, and because belinostat may cause teratogenicity and/or embryo-fetal lethality by virtue of targeting actively dividing cells, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 6 months after the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of belinostat and SGI-110 (guadecitabine) or ASTX727 administration Patients must be able to understand and willing to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible Exclusion Criteria: Patients with dedifferentiated, mesenchymal, or clear cell chondrosarcoma are not eligible Patients who have not recovered from adverse events (AEs) (i.e., have residual toxicities > grade 1) due to prior anti-cancer therapy are not allowed, with the exceptions of alopecia and endocrinopathies from prior immunotherapy-based treatments that are well-controlled with hormone replacement. In addition, the following time periods must elapse between the last dose of prior anti-cancer treatment and initiation of study treatment on this protocol: Cytotoxic chemotherapy or biologic, including immunotherapy: 28 days Small molecule targeted drug: 21 days or 5 half-lives, whichever is shorter. If 5 half-lives is shorter than 21 days, then 21 days applies. Radiation: 28 days, except for palliative radiation, for which 14 days applies Patients who are receiving any other investigational agents Patients with known history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to SGI-110 (guadecitabine), its active metabolite decitabine, or ASTX727, or belinostat Chronic use of any medications or substances that are strong inhibitors of UGT1A1 is not allowed. Patients must switch to alternative medications 7-14 days before treatment with belinostat. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product Patients with any known UGT1A1 polymorphism, heterozygous or homozygous, associated with reduced function (UGT1A1*6, UGT1A1*28, or UGT1A1*60) Patients with uncontrolled intercurrent illness Patients with psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because SGI-110 (guadecitabine) is a derivative of decitabine, and ASTX727 contains the agent decitabine, which has the potential for teratogenic or abortifacient effects, and because belinostat may cause teratogenicity and/or embryo-fetal lethality by virtue of targeting actively dividing cells. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with SGI-110 (guadecitabine), ASTX727 and belinostat, breastfeeding should be discontinued Prolongation of the heart-rate corrected QT (QTc) interval >= 450 ms (i.e., grade 1 or higher) on the screening electrocardiogram (ECG) prior to initiation of study treatment. If baseline QTc on screening ECG is >= 450 ms (i.e., grade 1 or higher): Check potassium and magnesium serum levels, and Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm a QTc interval < 450 ms
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mia Weiss
Organizational Affiliation
Yale University Cancer Center LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Hospital in Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC Norris Oncology/Hematology-Newport Beach
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
UCHealth University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Coral Gables
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Plantation
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
HaysMed University of Kansas Health System
City
Hays
State/Province
Kansas
ZIP/Postal Code
67601
Country
United States
Facility Name
University of Kansas Cancer Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Lawrence Memorial Hospital
City
Lawrence
State/Province
Kansas
ZIP/Postal Code
66044
Country
United States
Facility Name
University of Kansas Cancer Center-Overland Park
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Ascension Via Christi - Pittsburg
City
Pittsburg
State/Province
Kansas
ZIP/Postal Code
66762
Country
United States
Facility Name
Salina Regional Health Center
City
Salina
State/Province
Kansas
ZIP/Postal Code
67401
Country
United States
Facility Name
University of Kansas Health System Saint Francis Campus
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
Facility Name
University of Kansas Hospital-Westwood Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Siteman Cancer Center at West County Hospital
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Truman Medical Centers
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
University of Kansas Cancer Center - North
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64154
Country
United States
Facility Name
University of Kansas Cancer Center - Lee's Summit
City
Lee's Summit
State/Province
Missouri
ZIP/Postal Code
64064
Country
United States
Facility Name
University of Kansas Cancer Center at North Kansas City Hospital
City
North Kansas City
State/Province
Missouri
ZIP/Postal Code
64116
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center-South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm
Citations:
PubMed Identifier
34552007
Citation
Sheikh TN, Chen X, Xu X, McGuire JT, Ingham M, Lu C, Schwartz GK. Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors. Mol Cancer Ther. 2021 Dec;20(12):2362-2371. doi: 10.1158/1535-7163.MCT-21-0066. Epub 2021 Sep 22.
Results Reference
derived

Learn more about this trial

Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma

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