35 Participants Needed

Decitabine + Cedazuridine for Solid Tumors

Recruiting at 1 trial location
JH
DW
Overseen ByDanielle Wendler
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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 level to assess optimal hypomethylation and toxicity (up to 35 patients total).

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.

What data supports the effectiveness of the drug Decitabine + Cedazuridine for solid tumors?

The combination of Decitabine and Cedazuridine has been shown to be effective in treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), with clinical responses observed in 60% of patients, including 21% achieving complete response. This suggests potential effectiveness in other cancers, including solid tumors, although specific data for solid tumors is still being studied.12345

Is the combination of Decitabine and Cedazuridine safe for humans?

The combination of Decitabine and Cedazuridine has been studied in patients with certain blood disorders, and common serious side effects included low white blood cell counts, low platelet counts, and fever with low white blood cell counts. These side effects are similar to those seen with Decitabine alone.45678

How is the drug Decitabine + Cedazuridine unique for treating solid tumors?

Decitabine + Cedazuridine is unique because it combines decitabine, a drug that inhibits DNA methylation (a process that can turn off genes), with cedazuridine, which helps increase the amount of decitabine that can be absorbed when taken by mouth. This oral combination makes it easier for patients to take compared to traditional intravenous administration.458910

Research Team

Dr. Nilo Azad, MD - Baltimore, MD ...

Nilofer S. Azad

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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.
See 3 more

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
See 3 more

Timeline

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

Treatment Details

Interventions

  • Cedazuridine
  • Decitabine
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Decitabine and CedazuridineExperimental Treatment2 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)

Find a Clinic Near You

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

Findings from Research

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.
[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.
[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]
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.
[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]

References

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. [2023]
[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]. [2023]
[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]. [2022]
Decitabine/Cedazuridine: First Approval. [2021]
Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]
[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia]. [2019]
The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. [2022]
Decitabine: a review of its use in older patients with acute myeloid leukaemia. [2021]
FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. [2023]
Decitabine for acute myeloid leukemia. [2018]