Belinostat + Guadecitabine/ASTX727 for Chondrosarcoma

Not currently recruiting at 46 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: UGT1A1 inhibitors

Disqualifiers: Pregnancy, Uncontrolled illness, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 28 days per cycle, repeated until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drug combinations to treat chondrosarcoma, a type of bone cancer that cannot be surgically removed and has spread to other parts of the body. The goal is to determine if combining belinostat with guadecitabine or ASTX727 (also known as Decitabine/Cedazuridine) can stop the cancer from growing or spreading. Suitable candidates for this trial have symptomatic chondrosarcoma that cannot be surgically removed. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must avoid chronic use of medications that strongly inhibit UGT1A1 and switch to alternatives 7-14 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of belinostat with either guadecitabine or ASTX727 has been tested for safety in earlier studies. In one study, 19 patients received these treatments, and researchers monitored safety by taking small tissue samples (biopsies) and checking for side effects.

Belinostat is already used for other conditions, providing some safety information. Guadecitabine and ASTX727 are chemotherapy drugs that often cause side effects like nausea or tiredness, but these are closely monitored.

Overall, these treatment combinations have been studied sufficiently to advance to more advanced testing, indicating a manageable safety profile in previous patients. However, like all treatments, risks and side effects may occur. Researchers carefully monitor trial participants to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Belinostat, Guadecitabine, and ASTX727 for treating chondrosarcoma because it offers a novel approach compared to standard treatments like surgery and chemotherapy. This combination therapy leverages epigenetic modulation, with Belinostat acting as a histone deacetylase inhibitor and Guadecitabine/ASTX727 functioning as DNA methyltransferase inhibitors. By targeting the cancer cells' epigenetic makeup, this treatment aims to reactivate tumor suppressor genes and enhance the effectiveness of the cancer-killing process. This strategy provides a fresh avenue for tackling chondrosarcoma, particularly for patients who have limited options with conventional therapies.

What evidence suggests that this trial's treatments could be effective for chondrosarcoma?

Research has shown that combining belinostat with either guadecitabine or ASTX727 may slow the growth and spread of chondrosarcoma, a type of bone cancer. In this trial, participants will receive belinostat with either guadecitabine or ASTX727. Belinostat blocks certain enzymes that cancer cells need to grow. Guadecitabine and ASTX727 are chemotherapy drugs that kill cancer cells or stop them from multiplying and spreading. Early results suggest this combination could be effective for patients whose cancer cannot be surgically removed and has spread to other parts of the body. ^{2 3 5 6 7}

Who Is on the Research Team?

Mia Weiss

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults (18+) with a type of bone cancer called conventional chondrosarcoma that can't be surgically removed and has spread. Participants must have at least one measurable tumor, may have had any number of prior treatments or none, but their disease should not be treatable by surgery. They need to be in fair health overall (ECOG <=2) and able to undergo biopsy.

Inclusion Criteria

My cancer diagnosis will be reviewed at the study site.

I have a tumor that can be measured and hasn't been treated with radiation.

I can safely undergo a biopsy as per my doctor's assessment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive guadecitabine or ASTX727 and belinostat in 28-day cycles

28 days per cycle, repeated until disease progression or unacceptable toxicity

5 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• ASTX727
• Belinostat
• Guadecitabine

Trial Overview The study tests belinostat combined with either guadecitabine or ASTX727 on patients with advanced chondrosarcoma. Belinostat blocks enzymes needed for cell growth; guadecitabine and ASTX727 are chemotherapy drugs aiming to kill or stop the spread of cancer cells.

How Is the Trial Designed?

Group I: Treatment (belinostat, guadecitabine, ASTX727) Experimental Treatment 7 Interventions

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.

ASTX727 is already approved in United States, European Union for the following indications:

Approved in United States as Inqovi for:

• Myelodysplastic Syndromes (MDS)

Approved in European Union as Inqovi for:

• Myelodysplastic Syndromes (MDS)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I study involving 21 patients with advanced chondrosarcoma, ivosidenib treatment resulted in a significant reduction of the oncometabolite D-2-hydroxyglutarate (2-HG) in all patients, indicating effective targeting of the mutant IDH1 enzyme.

The treatment demonstrated minimal toxicity, with most adverse events being mild (grade 1 or 2), and a median progression-free survival of 5.6 months, suggesting potential for durable disease control in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. Tap, WD., Villalobos, VM., Cote, GM., et al.[2021]

In a phase 2 study involving 47 patients with unresectable or metastatic conventional chondrosarcoma, pazopanib demonstrated a disease control rate of 43% at 16 weeks, indicating its potential effectiveness in managing this type of cancer.

The median overall survival for patients was 17.6 months, with manageable side effects, primarily hypertension (26%) and elevated liver enzymes (9%), suggesting that pazopanib is a relatively safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. Chow, W., Frankel, P., Ruel, C., et al.[2021]

The combination of belinostat with cisplatin and etoposide (C+E) is safe and shows activity in treating advanced small cell lung cancer (SCLC), with 39% of patients responding positively to the treatment.

The study identified a maximum tolerated dose for the combination therapy and highlighted the importance of genotyping patients for UGT1A1 variants, as those with more than three copies had higher serum levels of belinostat, which could influence treatment outcomes and adverse event risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung. Balasubramaniam, S., Redon, CE., Peer, CJ., et al.[2020]

Chondrosarcoma, particularly in its metastatic or unresectable forms, is challenging to treat due to resistance to standard anticancer therapies, highlighting the need for novel treatments.

Recent research has identified promising biomarkers like IDH1/2 and COL2A1, and several targeted therapies and immunotherapies have shown encouraging antitumor activity in clinical studies for advanced chondrosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma. Miwa, S., Yamamoto, N., Hayashi, K., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11531

ETCTN/NCI 10330: A phase 2 study of belinostat with SGI- ... A phase 2 study of belinostat and SGI-110 (guadecitabine) for the treatment of unresectable and metastatic conventional chondrosarcoma. Jay ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04340843

Testing the Combination of Belinostat and SGI-110 ... Giving belinostat in combination with guadecitabine or ASTX727 may lower the chance of unresectable and metastatic chondrosarcoma growing or spreading. Detailed ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11526

Correlative results from NCI CTEP/ETCTN 10330: A phase ... Here we report correlative analysis of NCI 10330. Methods: NCI 10330 is a single-arm, multicenter, phase 2 study of belinostat with SGI-110 or ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT407966

A phase 2 study of belinostat with SGI-110 (guadecitabine ... A phase 2 study of belinostat and SGI-110 (guadecitabine) for the treatment of unresectable and metastatic conventional chondrosarcoma. First Author: Jay ...

5. csfshayna.org csfshayna.org/site/testing-the-combination-of-belinostat-and-sgi-110-guadecitabine-for-the-treatment-of-unresectable-and-metastatic-conventional-chondrosarcoma/

Testing the Combination of Belinostat and SGI-110 ... Giving belinostat in combination with guadecitabine may lower the chance of unresectable and metastatic chondrosarcoma growing or spreading. PRIMARY OBJECTIVE:.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04340843?cond=guadecitabine&viewType=Table&rank=10

Study Details | Testing the Combination of Belinostat and SGI- ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

7. mayo.edu mayo.edu/research/clinical-trials/cls-20504979

A Study to Evaluate Belinostat and Guadecitabine or ... The purpose of this study is to assess how well belinostat and SGI-110 (guadecitabine) or ASTX727 work in treating patients with conventional chondrosarcoma ...