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Trial record 24 of 219 for:    Oral Cancer | Recruiting Studies | NIH

The Immune Checkpoint Inhibitor Pembrolizumab in Combination With Oral Decitabine and Tetrahydrouridine as First-Line Therapy for Inoperable, Locally Advanced or Metastatic Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03233724
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : January 4, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


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.


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.


People 18 years and older who have NSCLC that cannot be removed by surgery


Participants will be screened with

  • Medical history
  • Physical exam
  • Blood and urine tests
  • Tests of heart and lung function

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 take the 2 study drugs by mouth 3-5 days a week.
  • Participants will get pembrolizumab in a vein for 30 minutes 1 day each cycle.

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Lung Cancer Non-Small Cell Lung Cancer Drug: Decitabine (DAC) Drug: Tetrahydrouridine (THU) Drug: Pembrolizumab Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Evaluation of the Immune Checkpoint Inhibitor, Pembrolizumab in Combination With Oral Decitabine and Tetrahydrouridine as First-Line Therapy for Inoperable, or Unresectable Locally Advanced or Metastatic Non-small Cell Lung Cancer
Actual Study Start Date : April 11, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: 2/Dose Expansion
DAC-THU + pembrolizumab at the dose established in Arm 1
Drug: Decitabine (DAC)
Administered orally at increasing frequency or dose from 3 - 5 times per week for 3 weeks

Drug: Tetrahydrouridine (THU)
Administered orally at increasing frequency or dose from 3 - 5 times per week for 3 weeks

Drug: Pembrolizumab
200 mg IV once a day every Wednesday or Thursday every 3 weeks.

Experimental: 1/Dose Escalation
DAC-THU + pembrolizumab at escalating doses
Drug: Decitabine (DAC)
Administered orally at increasing frequency or dose from 3 - 5 times per week for 3 weeks

Drug: Tetrahydrouridine (THU)
Administered orally at increasing frequency or dose from 3 - 5 times per week for 3 weeks

Drug: Pembrolizumab
200 mg IV once a day every Wednesday or Thursday every 3 weeks.

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: After 3 weeks at cycle 1 at each dose level dose level ]

  2. Overall response rate [ Time Frame: Every 9 weeks until at disease progression ]
    determine if this combination is associated with a response rate which exceeds that of Pembrolizumab alone in patients who have PD-Ll expression of at least 50 % and those who do not

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Patients must have histologically or cytologically confirmed, inoperable or unresectable, locally advanced, or metastatic NSCLC
  • Patients who have received no prior systemic treatment.
  • Patients must have analysis of PD-L1 expression in cancer cells quantitated by immunohistochemistry analysis.
  • Patients in Cohort 1 (dose escalation) may have any level of expression
  • Patients in Cohort 2 (high PD-L1) must have greater than or equal to 50% expression
  • Patients in Cohort 3 (low PD-L1) must have 0-49% expression
  • Patients must have measurable disease, per RECIST 1.1.
  • Willingness to undergo tumor biopsies if safely accessible per 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.
  • 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 FEV1 and DLCO greater than or equal to 35% predicted; oxygen saturation equal to or greater than 90% on room air by pulse oximetry or 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:

    • leukocytes greater than or equal to 3,000/mcL
    • absolute neutrophil count greater than or equal to 1,500/mcL (without transfusion or cytokine support)
    • absolute lymphocyte count greater than or equal to 800/mcL
    • platelets greater than or equal to 100,000/mcL
    • PT no more than 2 seconds above the ULN
    • total bilirubin < 1.5 X institutional upper limit of normal OR direct bilirubin less than or equal to ULN for patients with total bilirubin > 1.5 ULN
    • serum albumin greater than or equal to 2.0 mg/dL
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional ULN
    • creatinine less than or equal to 1.6 mg/ml OR creatinine clearance (eGFR) greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal at the time DAC-THU and pembrolizumab treatment commences.
  • 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 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 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 must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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, she should inform her treating physician immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document.


  • Patients with lung cancers harboring any targetable mutation for which there is approved for first line therapy.
  • Clinically significant cardiovascular / cerebrovascular disease as follows: cerebral vascular accident / stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class greater than or equal to II), serious cardiac arrhythmia, clinically significant bleeding or clinically significant pulmonary embolism
  • Active Hepatitis A, Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness due to unknown effects of DAC-THU on systemic immunity.
  • Other active infection requiring systemic therapy.
  • Pregnant women are excluded from this study because DAC-THU may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DACTHU, breastfeeding should be discontinued if the mother is treated with DAC-THU. These potential risks may also apply to other agents used in this study
  • Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
  • Patients who are receiving systemic corticosteroids.
  • Patients with history of or active autoimmune disease including thyroiditis, colitis, nephritis, neuropathy or pneumonitis.
  • Patients receiving another investigational agent.
  • An additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in-situ cervical or anal cancer, or ductal carcinoma in-situ
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Thrombocytosis defined as platelet count >1,200,000/mcL.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03233724

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Contact: Tricia Kunst, R.N. (240) 760-6234

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: David S Schrump, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT03233724     History of Changes
Other Study ID Numbers: 170140
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Demethylating Agents and Histone Deacetylase (HDAC) Inhibitors
DNA Hypomethylating Agent
Cytidine Deaminase
Checkpoint Inhibitor

Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors