Status and phase
Conditions
Treatments
About
Background:
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Lung cancer is the leading cause of cancer-related death in the United States. Most people with lung cancer are already in the advanced stages of the disease by the time they see a doctor. Researchers want to see if combining an approved drug with two new drugs can help.
Objective:
To study if tetrahydrouridine-decitabine (THU-DAC) with pembrolizumab is safe and effective in people with non-small cell lung cancer that cannot be removed by surgery.
Eligibility:
People 18 years and older who have NSCLC that cannot be removed by surgery
Design:
Participants will be screened with
They may have a small tumor sample taken (biopsy). They may have tumor scans.
Before starting treatment, participants will repeat the screening tests. They will also give a stool sample.
The study will be done in 3-week cycles for up to 6 cycles.
Participants will keep a study medication diary.
During cycle 1, participants will have blood taken multiple times on days 1 and 2.
Every 3 cycles, participants will repeat screening tests.
Participants will have a mandatory tumor biopsy.
When they finish treatment, participants will have a physical exam and blood tests.
Full description
Background:
Objectives:
Phase I
-To define pharmacokinetics, toxicities and maximum tolerated dose of oral DAC-THU in combination with pembrolizumab in patients with inoperable, or unresectable locally advanced or metastatic NSCLC, EsC, or MPM.
Phase II
-To determine clinical response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria to oral DAC-THU in combination with pembrolizumab in patients with inoperable, or unresectable, locally advanced or metastatic NSCLC, EsC, or MPM.
Eligibility:
Inclusion Criteria
Exclusion Criteria
Design:
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
INCLUSION CRITERIA:
Histologically or cytologically confirmed, inoperable or unresectable, locally advanced, or metastatic non-small cell lung cancers (NSCLC) or esophageal cancers including Seiwert-Stein Type I and Type II gastro-esophageal junction (GEJ) carcinomas, or malignant pleural mesothelioma (MPM).
NSCLC patients with no prior systemic treatment or those with prior first line treatment including an immune checkpoint inhibitor, are eligible for study.
Patients with esophageal and gastro-esophageal junction (GEJ) cancers are potentially eligible for study if they have received or refused first line standard of care cytotoxic therapy, and subsequent targeted therapy if appropriate.
Patients with MPM are eligible for study if they have received, refused or are ineligible for first line chemotherapy.
Patients who received deoxyribonucleic acid (DNA) demethylating agents or Programmed cell death protein 1 (PD-1)/Programmed Cell Death Ligand 1 (PD-L1)/PD-L1 inhibitors for another malignancy may be eligible for study if there were no dose-limiting immune related events, and there has been either no clinical evidence of disease or minimal residual disease that has been stable for at least three years.
Patients must have analysis of PD-L1 expression in cancer cells quantitated by immunohistochemistry analysis.
Measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Willingness to undergo tumor biopsies if safely accessible per principal investigator (PI) discretion before and after treatment.
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of Decitabine (DAC) and Tetrahydrouridine (THU) in combination with Pembrolizumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
Patients must be without evidence of unstable or decompensated myocardial disease; and must have adequate pulmonary reserve evidenced by Forced expiratory volume in the first second (FEV1) and diffusing capacity of lung for carbon monoxide (DLCO) greater than or equal to 35% predicted; oxygen saturation equal to or greater than 90% on room air by pulse oximetry or arterial blood gas (ABG) (to be drawn if pulse oximetry < 90% on room air)
No immunosuppressive medications except non-systemic corticosteroids
Patients must have normal organ and marrow function as defined below:
Patients with history of brain metastases except those with meningeal carcinomatosis or leptomeningeal disease may be eligible for treatment a minimum of 1 week following completion of gamma knife or whole brain radiotherapy, or 4 weeks following surgical resection of brain metastasis provided post-treatment magnetic resonance (MR) scan reveals no evidence of active disease, and no ongoing need for systemic steroids.
Patients with laboratory evidence of autoimmune disease (e.g., positive anti-nuclear antibodies (ANA) or lupus anticoagulant) without associated symptoms; vitiligo, or mild autoimmunity not impacting the function of organs, such as Hashimoto or psoriasis may be eligible for study.
The effects of DAC-THU and pembrolizumab on the developing human fetus are unknown. For this reason and because antineoplastic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men who engage in sexual activity must agree to use 2 forms of contraception at least 1 of which must be highly effective (intrauterine device [IUD], hormonal, tubal ligation; not highly effective includes barrier method) prior to study entry, for the duration of study participation and for 60 days after completion of the study treatment. Should a woman become pregnant, or suspect she is pregnant, while she or her partner is participating in this study the study participant should inform the study physician immediately.
Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Primary purpose
Allocation
Interventional model
Masking
9 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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