Decitabine/Cedazuridine (INQOVI), an Oral DNA Demethylating Agent, in Subjects With BAP1 Cancer Predisposition Syndrome and Subclinical, Early-Stage Mesothelioma

NCT05960773 | Suspended Phase 2 FDA Drug

• 2 other identifiers: 10001549001549-C
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II study to determine the rate of stabilization or disease improvement from investigational decitabine/cedazuridine (INQOVI) treatment in subjects with BRCA1-Associated Protein-1 (BAP1) Cancer Predisposition Syndrome (CPDS) and subclinical, early-stage mesothelioma. Progression-free survival (PFS) will also be determined for treated subjects, and the treatment safety (toxicity) evaluated....

Conditions

Mesothelioma; Early-stage Mesothelioma; Subclinical Mesothelioma; BRCA1-Associated Protein-1 (BAP1) Mutations; Early-stage BAP1-associated Malignancies; Malignant Mesothelioma (MM)

Keywords

BRCA1-Associated Protein-1; CPDS; DNA methyltransferases (DNMT); DNMT1; ring finger domains 1 (UHRF1); germline antigens; peripheral immune subsets

Outcome Measures

Primary Outcomes (1)

• To determine stabilization or disease improvement rates in participants with early-stage mesotheliomas arising in the context of BAP1 CPDS following decitabine/cedazuridine treatment

  Assessment of thoracoscopy and/or laparoscopy findings demonstrating stability of evaluable disease or improvement compared to baseline

  baseline, before each cycle, after every 6 treatment cycles (Course 1 and Course 2), and at the safety visit

Secondary Outcomes (2)

• To evaluate the safety of decitabine/cedazuridine

  before each cycle, after every 6 treatment cycles (Course 1 and Course 2), and at the safety visit

• To determine PFS in participants receiving decitabine/cedazuridine

  baseline, after every 6 treatment cycles (Course 1 and Course 2), and until date of progression or last visit ending at the time of the safety visit

Study Arms (1)

1/ Arm 1

EXPERIMENTAL

Decitabine/cedazuridine (35 mg decitabine and 100 mg cedazuridine; PO QD)

Drug: Decitabine/cedazuridine

Interventions

Decitabine/cedazuridine DRUG

Decitabine/cedazuridine (INQOVI) oral tablet (35 mg decitabine and 100 mg cedazuridine) taken 3 consecutive days during the first week of every cycle (1 cycle=28-days) for 6 cycles (i.e., 1 course). Additional 6 cycles (i.e., Course 2) for subjects with stable disease or disease regression. Max (total) of 2 treatment courses.

1/ Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with history of germline BRCA1-Associated Protein-1 (BAP1) mutations.
• Histologically confirmed by NCI LP subclinical, early-stage (Tx-T1) mesotheliomas.
• Participants with other early-stage BAP1-associated malignancies in addition to subclinical, early-stage mesotheliomas are eligible for study.
• The extent of the disease (Tx by radiographic imaging) must be insufficient to warrant approved front-line therapies (surgery, chemotherapy, immunotherapy) per standard of care (SOC). Participants with cT1 tumors may be eligible for study if they have been offered and have refused front-line SOC treatment.
• Age \>= 18 years.
• Evaluable disease as confirmed by minimally invasive (videoscopic) assessment (thoracoscopy and/or laparoscopy) performed at screening (within 8 weeks prior to treatment initiation).
• Willingness to undergo pre- and post-treatment minimally invasive thoracoscopy and/or laparoscopy to assess treatment response.
• Willingness to co-enroll on 20C0106 (Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients with BAP1 Tumor Predisposition Syndrome) and/or 06C0014 (Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) to enable collection/processing of tumor, blood and normal pleura if applicable per PI.
• ECOG performance status 0 - 1
• Adequate pulmonary reserve evidenced by FEV1 and DLCO \>= 35% predicted on screening pulmonary function testing (PFTs).
• Oxygen saturation \>= 92% on room air by pulse oximetry at screening.
• Adequate renal, hepatic, and hematopoietic function at screening as defined below:
• leukocytes \>= 3,000/microL
• absolute neutrophil count \>= 1,500/microL (without transfusion or cytokine support within 2 months prior to study treatment initiation)
• absolute lymphocyte count \> 800/microL

You may not qualify if:

• Participants with cancers requiring frontline standard of care treatment.
• Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to study treatment initiation), myocardial infarction (\< 6 months prior to study treatment initiation), unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II, serious cardiac arrhythmia, clinically significant bleeding or clinically significant pulmonary embolism.
• Therapeutic anticoagulation within 2 weeks prior to study treatment initiation.
• Active Hepatitis A (HAV), Hepatitis B (HBV) (e.g., HBsAg reactive), or Hepatitis C (HCV) (e.g., HCV RNA \[qualitative\] is detected) at screening.
• History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
• Other active infections requiring systemic therapy.
• Active COVID infection.
• Major surgery within 4 weeks prior to study treatment initiation.
• Immunosuppressive medications within 4 weeks prior to study treatment initiation except non-systemic corticosteroids.
• History of prior treatment with a DNA demethylating agent.
• Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in IOCBP at screening).
• Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mesothelioma; Mesothelioma, Malignant

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• David S Schrump, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2023
• First Posted: July 27, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-06-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers within 10 years after the completion of the primary endpoint by contacting the Principal Investigator.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)