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Locally Advanced Unresectable Primary Central ChondrosarcomaPhase 2NCT04340843

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

A Phase 2 study testing Belinostat, Biopsy Procedure and Biospecimen Collection in people with Locally Advanced Unresectable Primary Central Chondrosarcoma and Metastatic Primary Central Chondrosarcoma, run by National Cancer Institute (NCI) at 39 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Belinostat, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
39 sitesUnited States
Study dates
8 Sep 2020to 27 Jan 2027
Phase
Phase 2

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 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

39 sites in 1 country.

39 sites in 1 country

United States39 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Northwestern University

    Chicago, Illinois, 60611

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • HaysMed

    Hays, Kansas, 67601

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06520

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Mercy Hospital Pittsburg

    Pittsburg, Kansas, 66762

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Health System Saint Francis Campus

    Topeka, Kansas, 66606

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Phase 2 Study of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Belinostat, Biopsy Procedure, Biospecimen Collection, Computed Tomography, Decitabine and Cedazuridine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelinostatDrug

    Also called Beleodaq, PXD 101, PXD-101, PXD101

    Given IV

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Decitabine and CedazuridineDrug

    Also called ASTX 727, ASTX-727, ASTX727, C-DEC

    Given PO

  • GuadecitabineDrug

    Also called DNMT inhibitor SGI-110, S110, SGI 110, SGI-110

    Given SC

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

Study groups in NCT04340843
Study groupRoleWhat they receive
Treatment (belinostat, guadecitabine, ASTX727)ExperimentalPatients 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.
Receives: Drug: Belinostat; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Decitabine and Cedazuridine; Drug: Guadecitabine; Procedure: Magnetic Resonance Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) in Belinostat, ASTX727

    Best Objective Response per RECIST Version 1.1 criteria. CR, complete response defined by the disappearance of all target lesions; PR, partial response defined by at least a 30% decrease in the sum of the diameters of target lesions; SD, stable disease defined by neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; PD, progressive disease defined by at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.

    Measured: Within 6 months after initiating study treatment

Secondary outcomes (5)

  1. Presence of Treatment Related Adverse Events (AEs) in Belinostat, ASTX727

    Adverse events (AEs) in belinostat, ASTX727 were recorded at each clinical visit and were 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 was recorded and categorized as possibly, probably, or definitely related to treatment. AEs are reported as counts and percentages per AE by grade and the number of patients with a given maximal grade of toxicity.

    Measured: Up to 24 months post treatment

  2. Progression Free Survival (PFS) in Belinostat, ASTX727

    PFS is defined as the time from first treatment with the study drug to the earliest of either disease progression or death from any cause. Patients who are alive and progression free will be censored at the time of their last follow-up. The Kaplan-Meier method was used to evaluate time to event endpoints. Median PFS was reported with a 95% confidence interval. Data will be presented as Kaplan Meier plots.

    Measured: 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.

  3. Presence of Treatment Related Adverse Events (AEs) in Belinostat, SGI-110

    Adverse events (AEs) from belinostat, SGI-110 were recorded at each clinical visit and were 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 was recorded and categorized as possibly, probably, or definitely related to treatment. AEs are reported as counts and percentages per AE by grade and the number of patients with a given maximal grade of toxicity.

    Measured: Up to 24 months post treatment

  4. Progression Free Survival (PFS) in Belinostat, SGI-110

    PFS is defined as the time from first treatment with the study drug to the earliest of either disease progression or death from any cause. Patients who are alive and progression free will be censored at the time of their last follow-up. The Kaplan-Meier method was used to evaluate time to event endpoints. Median PFS was reported with a 95% confidence interval. Data will be presented as Kaplan Meier plots.

    Measured: 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.

  5. Objective Response Rate (ORR) in Belinostat, SGI-110

    Best Objective Response per RECIST Version 1.1 criteria. CR, complete response defined by the disappearance of all target lesions; PR, partial response defined by at least a 30% decrease in the sum of the diameters of target lesions; SD, stable disease defined by neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; PD, progressive disease defined by at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.

    Measured: Within 6 months after initiating study treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2020
  2. Study start8 Sep 2020
  3. Primary completion22 Feb 2024
  4. Study completion27 Jan 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04340843
Sponsor's protocol ID
NCI-2020-02187
Other IDs
NCI-2020-02187, 10330, 10330, UM1CA186686
Status last verified
Jul 2026
First submitted
9 Apr 2020
Last updated
8 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 34552007

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