Trial · NCT03233724
Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas
NCT03233724, Phase 1, Phase 2, Terminated, National Cancer Institute (NCI); results first posted 2023-05-31
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas. Trials, record NCT03233724. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03233724
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
Oral Decitabine and Tetrahydrouridine as Epigenetic Priming for Pembrolizumab-Mediated Immune Checkpoint Blockade in Patients With Inoperable, or Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancers and Esophageal Carcinomas
- NCT number
- NCT03233724
- Status
- Terminated
- Phases
- Phase 1, Phase 2
- Enrollment
- 9 participants, actual
- Lead sponsor
- National Cancer Institute (NCI)
- Conditions
- Carcinoma, Non-Small-Cell Lung, Lung Cancer, Non-Small Cell Lung Cancer, Carcinoma, Esophageal, Malignant Pleural Mesotheliomas
- Interventions
- Decitabine (DAC), Tetrahydrouridine (THU), Pembrolizumab
- First posted
- 2017-07-31
- Last updated
- 2023-05-31
- Results first posted
- 2023-05-31
Source ClinicalTrials.gov
Registered outcomes9
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Overall Response Rate | Every 10 weeks (± 1 week) until disease progression or unacceptable toxicity or off study criteria is met. Longest participant on study 11 months. | Overall response rate was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine if the combination of decitabine and tetrahydrouridine is associated with a response rate which exceeds that of Pembrolizumab alone in participants who have programmed death-ligand 1 (PD-L1) expression of at least 50% and those who do not. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. |
| Primary | Maximum Tolerated Dose (MTD) of Decitabine | Within the first 6 weeks (two cycles) | Maximum Tolerated Dose (MTD) is the maximum dose at which fewer than one-third of participants experience dose limiting toxicity (DLT) within the first 6 weeks (two cycles) of decitabine and tetrahydrouridine therapy. If one of three patients at any given dose level experiences DLT, up to three additional patients will be treated at this dose level. If only one of six patients exhibit DLT, subsequent patients will be enrolled into the next higher dose level. As soon as two patients at any given dose level develop DLT, no additional patients will be entered at that level. Subsequent patients will be accrued into the preceding dose level; if DLT is observed in less than two of six patients treated at this lower level, this dose will represent maximum tolerated dose (MTD). A DLT is any Grade 3 or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness. |
| Primary | Maximum Tolerated Dose (MTD) of Tetrahydrouridine | Within the first 6 weeks (two cycles) | Maximum Tolerated Dose (MTD) is the maximum dose at which fewer than one-third of participants experience dose limiting toxicity (DLT) within the first 6 weeks (two cycles) of decitabine and tetrahydrouridine therapy. If one of three patients at any given dose level experiences DLT, up to three additional patients will be treated at this dose level. If only one of six patients exhibit DLT, subsequent patients will be enrolled into the next higher dose level. As soon as two patients at any given dose level develop DLT, no additional patients will be entered at that level. Subsequent patients will be accrued into the preceding dose level; if DLT is observed in less than two of six patients treated at this lower level, this dose will represent maximum tolerated dose (MTD). A DLT is any Grade 3 or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness. |
| Secondary | Changes in Circulating Tumor Cells (CTCs) | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | Peripheral blood will be collected to correlate changes in circulating tumor cells with clinical response. CTCs will be assessed using ferrofluidic enrichment and multi-parameter flow cytometric detection. Baseline and post-treatment specimen collection after one course of therapy (Week 10 +/- one week). |
| Secondary | Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC) | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | Peripheral blood mononuclear cells (PBMC) will be assessed using multiparameter flow cytometry for immune subsets including but not necessarily limited to Tregs, myeloid-derived suppressor cells (MDSC), effector and exhausted cluster of differentiation 4 (CD4+), cytotoxic T lymphocytes (CD8+) T cells, and cluster of differentiation 14 (CD14 +) monocytes. Assessment will include functional markers, i.e., programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), cluster of differentiation 152 (CTLA-4), human leukocyte antigen (HLA) membrane heterodimeric glycoproteins (-DR) and/or cluster of differentiation 40 (CD40). Baseline and post-treatment specimen collection after one course of therapy (Week 10 +/- one week). |
| Secondary | Percent Viable Tumor Cells | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | Portions of biopsy materials will be sent for frozen section or permanent section confirmation of malignancy, i.e., non-small cell lung cancers (NSCLC), esophageal carcinomas (Esc), malignant pleural mesothelioma (MPM) cells, and percent viable tumor cells. All of the analyses are predicated on acquisition of sufficient materials. |
| Secondary | Changes in Gene, Endogenous Retroviral (ERV), Micro Ribonucleic Acid (RNA) Expressions, Deoxyribonucleic Acid (DNA) Methylation Signatures and Tumor Microenvironment | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | Tissue will be processed for focused gene, endogenous retroviral and microRNA expressions, and DNA methylation signatures using quantitative reverse-transcription polymerase chain reaction (RT-PCR), nanostring, pyrosequencing and digital droplet PCR techniques. Isolate serum for focused methylation analysis. If sufficient tissue is available, another portion will be imbedded in paraffin for subsequent immunostaining experiments, focusing on expression of genes focusing on those proteins encoded by genes that have been identified to be clearly activated by epigenetic therapy. If sufficient materials are present, additional more comprehensive analyses including multiplex immunohistochemistry analysis of tumor microenvironment may be performed with the focus of materials from participants treated at the maximum tolerated dose. All of the analyses are predicated on acquisition of sufficient materials. |
| Other | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
| Other | Number of Participants With a Dose Limiting Hematologic Toxicity (DLT) | First two cycles of Course 1 of therapy | A DLT is any Grade 3 (severe) or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness. |
Source ClinicalTrials.gov
Outcomes9
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Overall Response Rate | Every 10 weeks (± 1 week) until disease progression or unacceptable toxicity or off study criteria is met. Longest participant on study 11 months. | 1/9 participants did not receive any therapy. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Maximum Tolerated Dose (MTD) of Decitabine | Within the first 6 weeks (two cycles) | 1/9 participants did not receive any therapy. | mg/kg | NUMBER |
| PRIMARY | Maximum Tolerated Dose (MTD) of Tetrahydrouridine | Within the first 6 weeks (two cycles) | Within the first 6 weeks (two cycles) | mg/kg | NUMBER |
| SECONDARY | Changes in Circulating Tumor Cells (CTCs) | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | This outcome measure was not evaluated and was to be performed in bulk. No assays were performed due to the pandemic. Participants could not travel to the National Institutes of Health (NIH) to have samples drawn. | ||
| SECONDARY | Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC) | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | This outcome measure was not evaluated and was to be performed in bulk. No assays were performed due to the pandemic. Participants could not travel to the National Institutes of Health (NIH) to have samples drawn. | ||
| SECONDARY | Percent Viable Tumor Cells | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | This outcome measure was not done because 1 participant declined biopsy due to the pandemic. And one participant did not have adequate tissue to evaluate. All other participants did not have biopsies. | ||
| SECONDARY | Changes in Gene, Endogenous Retroviral (ERV), Micro Ribonucleic Acid (RNA) Expressions, Deoxyribonucleic Acid (DNA) Methylation Signatures and Tumor Microenvironment | Baseline and post-treatment after one course of therapy (Week 10 +/- one week) | This outcome measure was not done because 1 participant declined biopsy due to the pandemic. And one participant did not have adequate tissue to evaluate. All other participants did not have biopsies. | ||
| OTHER_PRE_SPECIFIED | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively. | 1/9 participants did not receive any therapy. | Participants | COUNT_OF_PARTICIPANTS |
| OTHER_PRE_SPECIFIED | Number of Participants With a Dose Limiting Hematologic Toxicity (DLT) | First two cycles of Course 1 of therapy | 1/9 participants did not receive any therapy. | Participants | COUNT_OF_PARTICIPANTS |
Source ClinicalTrials.gov
Results by group27
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | Complete Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | Complete Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | Complete Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | Partial Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | Partial Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | Partial Response | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | Stable Disease | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | Stable Disease | 0 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | Stable Disease | 1 | Participants | |
| Overall Response Rate | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | Progressive Disease | 0 | Participants |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 results by groupParticipant flow30
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Phase I Dose Escalation | STARTED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 2 | |
| Phase I Dose Escalation | STARTED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 2 | |
| Phase I Dose Escalation | STARTED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 4 | |
| Phase I Dose Escalation | STARTED | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | |
| Phase I Dose Escalation | STARTED | Enrolled to Revised Dose Level 1 But Not Treated | 1 | |
| Phase I Dose Escalation | COMPLETED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 1 | |
| Phase I Dose Escalation | COMPLETED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 1 | |
| Phase I Dose Escalation | COMPLETED | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 1 | |
| Phase I Dose Escalation | COMPLETED | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | |
| Phase I Dose Escalation | COMPLETED | Enrolled to Revised Dose Level 1 But Not Treated | 0 |
1 to 10 of 30Source ClinicalTrials.gov
See all 30 participant flowAdverse events132
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Activated partial thromboplastin time prolonged | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 0 | 2 | 0 |
| other | Activated partial thromboplastin time prolonged | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 0 | 2 | 0 |
| other | Activated partial thromboplastin time prolonged | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 1 | 4 | 1 |
| other | Activated partial thromboplastin time prolonged | Investigations | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | 0 | 0 |
| other | Alkaline phosphatase increased | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 0 | 2 | 0 |
| other | Alkaline phosphatase increased | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 0 | 2 | 0 |
| other | Alkaline phosphatase increased | Investigations | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 2 | 4 | 4 |
| other | Alkaline phosphatase increased | Investigations | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | 0 | 0 |
| other | Anemia | Blood and lymphatic system disorders | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 1 | 2 | 7 |
| other | Anemia | Blood and lymphatic system disorders | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 1 | 2 | 1 |
1 to 10 of 132Source ClinicalTrials.gov
See all 132 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 0 | 2 |
| Total, all-cause mortality | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 0 | 2 |
| Total, all-cause mortality | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | 4 |
| Total, all-cause mortality | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | 0 |
| Total, other adverse events | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 2 | 2 |
| Total, other adverse events | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 2 | 2 |
| Total, other adverse events | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 4 | 4 |
| Total, other adverse events | Decitabine 0.17mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks | 0 | 0 |
| Total, serious adverse events | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT) | 2 | 2 |
| Total, serious adverse events | Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT) | 1 | 2 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
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