Decitabine + Cedazuridine for Solid Tumors

Recruiting at 1 trial location

Overseen By Danielle Wendler

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Investigational agents

Disqualifiers: Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle, up to 2 years

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of two drugs, cedazuridine and decitabine, for individuals with inoperable, metastatic solid tumors. The goal is to determine the optimal dose and identify any side effects. Those who have tried at least two other cancer treatments without success may qualify. Participants must be able to swallow pills and have a measurable tumor for monitoring changes during the trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be on any other investigational agents and must not have had chemotherapy or radiotherapy within the last 3 weeks.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of decitabine and cedazuridine has been tested for safety in previous studies. The FDA has approved this combination for treating certain blood disorders, indicating it is generally considered safe. In those studies, the combination treated blood-related conditions and was mostly well-tolerated, with most patients not experiencing severe side effects.

However, this is an early-phase study for solid tumors. Early-phase trials often focus on checking safety and finding the right dose, so there might still be unknowns about the combination's effectiveness for solid tumors. Participants in this trial will help researchers learn more about the safety of these drugs in this new setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Decitabine and Cedazuridine for treating solid tumors because this combination has a unique mechanism of action. Unlike conventional chemotherapy, which often targets fast-dividing cells indiscriminately, Decitabine acts as a DNA methylation inhibitor, potentially reactivating silenced genes that suppress tumors. Cedazuridine enhances the effectiveness of Decitabine by preventing its breakdown in the body, allowing for oral administration instead of traditional intravenous methods. This not only improves patient convenience but also opens the door to more consistent dosing and potentially fewer side effects.

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

Research shows that combining decitabine and cedazuridine yields promising results for certain blood cancers. In one study, patients lived for a median of 31.7 months, with 62% responding to the treatment. The pill form of this treatment matches the effectiveness of the IV version, delivering nearly 99% of the drug's benefits. Although this research focuses on blood cancers, the way decitabine alters DNA to halt cancer and cedazuridine enhances its efficacy suggests potential benefits for solid tumors. This trial will specifically evaluate the combination of decitabine and cedazuridine for solid tumors. Early results appear hopeful, but further research is needed to confirm its effectiveness for solid tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Nilofer S. Azad

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who've tried at least two treatments without success or declined other beneficial therapies. They must be in good physical condition (ECOG <1), able to swallow pills, and have measurable tumor growth. People can't join if they have recent ulcers, bowel blockages, chemotherapy or radiotherapy within the last 3 weeks, are on other experimental drugs, or have active hepatitis B/C or symptomatic ascites.

Inclusion Criteria

I can swallow pills.

My cancer is advanced, cannot be surgically removed, and has spread.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

I have an active hepatitis B or C infection.

I have had fluid build-up in my abdomen causing discomfort in the last 4 weeks.

Participants may not be receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of cedazuridine and decitabine on an outpatient basis. Cycle length is 28 days.

28 days per cycle, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cedazuridine
• Decitabine

Trial Overview The study tests different doses of Cedazuridine combined with Decitabine in patients with solid tumors to find the best dose that modifies DNA methylation without causing too much toxicity. At least six people will be tested per dose level up to a total of thirty participants.

How Is the Trial Designed?

Group I: Decitabine and Cedazuridine Experimental Treatment 2 Interventions

Treatment will be administered on an outpatient basis. Cycle length is 28 days. The dose of cedazuridine is fixed at 100mg and the dose and duration of decitabine will vary depending on when a patient enters the study.

Cedazuridine is already approved in United States for the following indications:

Approved in United States as ASTX727 for:

• Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Astex Pharmaceuticals, Inc.

Industry Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

Decitabine, administered at a dose of 20 mg/m² for 5 consecutive days, has been approved for older patients (≥65 years) with acute myeloid leukaemia (AML) who cannot undergo standard treatment, showing clinically meaningful improvements in overall survival after extended follow-up.

In a pivotal phase III trial, decitabine demonstrated significantly higher complete remission rates compared to standard treatment options like cytarabine, with a safety profile similar to cytarabine, including common side effects like fever and low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. Curran, MP.[2021]

Oral azacitidine (CC-486) has been shown to improve overall survival as maintenance therapy for older patients with acute myeloid leukemia who are in complete remission, highlighting its efficacy in this specific patient population.

The combination of decitabine and cedazuridine (ASTX727) is approved for treating adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, particularly those with intermediate-1 or higher risk, indicating its targeted therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. Kipp, D., H Wei, A.[2022]

In a study of 45 elderly patients (average age 68.5) with high-risk MDS and MDS-transformed AML, the decitabine combined with CEG regimen (DCEG) showed a significantly higher overall response rate (86.4%) compared to the decitabine combined with CAG regimen (47.8%).

Patients treated with the DCEG regimen also experienced longer overall survival (10 months) and progression-free survival (9 months) compared to those on the CAG regimen, indicating that DCEG may be a more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen]. Wu, M., Ma, IX., Xie, YH., et al.[2022]

In a study of 8 geriatric patients with acute myeloid leukemia, treatment with decitabine, with or without low-dose cytarabine, resulted in a 50% overall response rate, with 25% achieving complete remission and 25% achieving partial remission.

The treatment showed a median overall survival time of 9.5 months, with some patients surviving over a year, although it was associated with significant side effects, including severe myelosuppression in 87.5% of patients and pneumonia in 50%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia]. Zhou, HW., Zhou, MH., Wang, ZH., et al.[2019]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

Decitabine is a DNA methyltransferase inhibitor with a long history of antileukemic efficacy, particularly effective in treating acute myeloid leukemia in older patients or those unable to undergo intensive therapy.

The current dosing regimen of decitabine (20 mg/m² for 5 days) has been refined to minimize nonhematologic toxicity, making it a promising option for patients who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. Marks, PW.[2018]

Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.

The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

The D-CAG regimen, which combines decitabine with a modified chemotherapy approach, achieved a complete remission (CR) rate of 69.4% in 59 elderly patients (≥70 years) with newly diagnosed acute myeloid leukemia (AML), indicating its efficacy in this age group.

The treatment was found to be safe, with major adverse reactions including grade 3-4 myelosuppression and infections, but it significantly improved overall survival (OS) and event-free survival (EFS) for patients who achieved CR, with median OS of 19.8 months compared to 6.4 months for those who did not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. Cao, L., Jiang, ZQ., Liu, WJ., et al.[2023]

In a study of 44 patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), the combination of decitabine with the EIAG regimen resulted in a higher modified composite complete response (mCRc) rate of 72.7% compared to 40.9% in the CAG regimen group, indicating improved efficacy.

Both treatment regimens led to significant myelosuppression as a common adverse effect, but there was no increase in non-hematological toxicities, suggesting that decitabine combined with EIAG is a safe option that enhances remission rates without adding extra risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome]. Mao, JP., Xue, LG., Zhu, YX., et al.[2023]

Citations

1. taihooncology.com taihooncology.com/us/news/2021-09-23_astex_press_release_astx727_mos_data_presented_at_mds_international_symposium/

Astex Pharmaceuticals Presents Overall Survival Data ... Study achieved median overall survival of 31.7 months; Updated efficacy data demonstrated an overall response rate of 62%, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03875287?term=CEDAZURIDINE%20AND%20DECITABINE&rank=2

NCT03875287 | Dose-Escalation Study of E7727, an Oral ... This is a phase 1 study of the combination of cedazuridine with decitabine in patients with solid tumors. At least 6 patients will be enrolled per treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8701430/

Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the ... Here, we present outcome data for this study for the enrolled subpopulation of patients with CMML. Methods: We used a randomized cross over ...

4. astx.com astx.com/taiho-oncology-and-astex-pharmaceuticals-present-overall-survival-data-for-oral-decitabine-and-cedazuridine-inqovi-astx727-in-patients-with-mds-and-cmml-harboring-tp53-mutations-at-64th-ash-a/

Taiho Oncology and Astex Pharmaceuticals Present ... The study found that a dosing schedule of 10 mg decitabine/100 mg cedazuridine daily for five days led to balanced clinical efficacy with an ...

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Oral Decitabine-Cedazuridine Is a Game Changer for ... Critically, the primary end point of total drug exposure was met, with the oral formulation achieving 98.93% (90% CI, 92.66%-105.60%) of the IV ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04953897

NCT04953897 | Study to Evaluate the Pharmacokinetics ... This is a Phase 1b, multicenter, open-label, PK, and safety study of multiple oral doses of oral decitabine and cedazuridine (formerly known as ASTX727) as ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7708383/

Decitabine/Cedazuridine: First Approval - PMC In July 2020, decitabine/cedazuridine received its first approval in the USA and Canada for the treatment of MDS and CMML.

8. astx.com astx.com/media-center/presentations-and-publications/astx727-hematological-malignancies/

Oral Decitabine and Cedazuridine (ASTX727) Oral Decitabine and Cedazuridine (ASTX727) – Hematologic Malignancies. 2019. 2019 ASH – Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01689

ASTX727 with or without DLI for the Treatment of Acute ... This phase I/II trial tests the safety, side effects, and best dose of decitabine and cedazuridine (ASTX727) with or without donor lymphocyte infusion (DLI) ...