SUSPENDED

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

Conditions

Mesothelioma Malignant Mesothelioma (MM)Early-stage Mesothelioma Subclinical Mesothelioma BRCA1-Associated Protein-1 (BAP1) Mutations Early-stage BAP1-associated Malignancies BRCA1-Associated Protein-1 CPDS DNA methyltransferases (DNMT)DNMT1 ring finger domains 1 (UHRF1)germline antigens peripheral immune subsets

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-01-31

Study Completion:2026-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT05960773

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * platelets \>=100,000/microL and \< 1,200,000/microL * prothrombin time (PT) \<=2 seconds above the upper limit of normal (ULN) * total bilirubin \< 1.5 X institutional upper limit of normal OR direct bilirubin \<= 1 ULN for participants with total bilirubin \> 1.5 ULN * serum albumin \>= 2.0 mg/dL * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<= 2.5 X institutional ULN * creatinine \<= 1.6 mg/ml OR creatinine clearance (eGFR) \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal. * Individuals of child-bearing potential (IOCBP) and those that can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization) from the study entry and up to 6 months (IOCBP) or 3 months (those that can father children) after the last dose of the decitabine/cedazuridine. * Nursing (including breastfeeding) participants must be willing to discontinue nursing from study treatment initiation through 2 weeks after the last dose of the study drug. * The ability of a participant to understand and the willingness to sign a written informed consent document.	* 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.

Inclusion Criteria

Exclusion Criteria

* 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
* platelets \>=100,000/microL and \< 1,200,000/microL
* prothrombin time (PT) \<=2 seconds above the upper limit of normal (ULN)
* total bilirubin \< 1.5 X institutional upper limit of normal OR direct bilirubin \<= 1 ULN for participants with total bilirubin \> 1.5 ULN
* serum albumin \>= 2.0 mg/dL
* aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<= 2.5 X institutional ULN
* creatinine \<= 1.6 mg/ml OR creatinine clearance (eGFR) \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.
* Individuals of child-bearing potential (IOCBP) and those that can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization) from the study entry and up to 6 months (IOCBP) or 3 months (those that can father children) after the last dose of the decitabine/cedazuridine.
* Nursing (including breastfeeding) participants must be willing to discontinue nursing from study treatment initiation through 2 weeks after the last dose of the study drug.
* The ability of a participant to understand and the willingness to sign a written informed consent document.

* 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.

Contacts and Locations

Principal Investigator

David S Schrump, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

David S Schrump, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-31

Study Completion Date2026-12-01

Study Record Updates

Study Start Date2024-01-31

Study Completion Date2026-12-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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