Metastatic Pancreatic AdenocarcinomaEarly Phase 1NCT02847000
p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Pancreatic Cancer
A Early Phase 1 study testing Tetrahydrouridine and Decitabine in people with Metastatic Pancreatic Adenocarcinoma, run by Yogen Saunthararajah at 2 sites in United States.
Trial summary
Patients with pancreatic cancer which has stopped responding to one or more chemotherapy drugs are asked to take part in this study. The study hopes to find out whether decitabine, the drug being studied, will have an effect on pancreatic cancer. The decitabine is being given at a lower dose than its approved use. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Adenocarcinoma
- What is being tested?
- Tetrahydrouridine and Decitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Dec 2016to 30 Oct 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically proven pancreatic carcinoma or adenocarcinoma. Histologies other than carcinoma/adenocarcinoma will not be eligible.
- Subjects must have received one or more prior systemic therapies for this disease, with disease progression or intolerable toxicity precluding further therapy with prior regimen(s).
- Measurable disease per RECIST 1.1.
- ECOG performance status 0 - 2
- Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x laboratory upper limit of normal (ULN)
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- Total serum bilirubin ≤ 2.0 x ULN
- Absolute neutrophil count (ANC) ≥ 1500/uL
- Platelets ≥ 75,000/uL
- Hemoglobin ≥ 8.0 g/dL
- Serum calcium ≤ 12.0 mg/dL
- Serum creatinine ≤ 2.9 mg/dL
- Eligible and agreeable for percutaneous biopsy of a primary or metastatic lesion prior to treatment and after approximately 16 weeks of treatment
- Patients with history of brain metastases can be enrolled at a minimum of 2 weeks following the completion of surgery, gamma knife or whole brain radiotherapy. Repeat brain MRI not required for eligibility.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
- At least two-weeks since receipt of prior standard or investigational therapy.
Who cannot join
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with oral THU-Dec. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
- Pregnancy or breastfeeding (pregnant or breastfeeding women are excluded from this study because oral THU-Dec has 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 oral THU-Dec, breastfeeding should be discontinued if the mother is treated with oral THU-Dec.
- 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.
- Receiving other investigational agent
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Advanced Pancreatic Cancer That Has Progressed Through One or More Lines of Therapy
Patients with pancreatic cancer which has stopped responding to one or more chemotherapy drugs are asked to take part in this study. The study hopes to find out whether decitabine, the drug being studied, will have an effect on pancreatic cancer. The decitabine is being given at a lower dose than its approved use. It is also being given with another drug, tetrahydrouridine (THU), to improve the exposure of your pancreatic cancer cells to decitabine.
The purpose of this study is to determine if the drug combination of decitabine and tetrahydrouridine can recognize a certain DNA target in your cancer. All cells have DNA within them, and tumor cells have abnormal DNA.
Read the detailed description
Primary Objective The primary goal of this pilot study is to detect decitabine therapy induced DNMT1 protein level decreases with an effect size of 1 using a paired t-test and alpha=0.05. The effect size is defined as the difference in mean DNMT1-protein levels between post-treatment and pre-treatment divided by the standard deviation and is thus a metric of change in the natural units of the distribution, its standard deviation. Our goal is thus to detect drops in DNMT1 of at least one standard deviation.
Secondary Objectives Secondary goals include correlating DNMT1 decreases with clinical response (measured by Response Evaluation Criteria in Solid Tumors [RECIST1.1]), using logistic regression; time to relapse, using a Cox model; tolerability and safety assessment by toxicity characterization using CTCAEv4.
Study Design Single-arm, open-label, proof-of-concept clinical trial in patients with metastatic pancreatic cancer that has progressed on one or more lines of systemic therapy.
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Being tested
- Tetrahydrouridine, Decitabine
- Keywords
- Decitabine, Tetrahydrouridine, Epigenetic Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TetrahydrouridineDrug
Also called THU
Starting dose is by weight:
THU is supplied as 250 mg/capsule Weight 40-60kg = 2 capsules of Tetrahydrouridine. Weight 61-80kg = 3 capsules of THU. Weight 81-100kg or higher = 4 capsules of THU.
Timing between THU and Dec, Frequency of administration: Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days. Treatment on protocol monitoring continues for 52 weeks, however, subjects will have the option to continue beyond this period if it judged to be in their interests.
DecitabineDrug
Also called DEC
Starting dose is by weight:
DEC is supplied as 5 mg/capsule. Weight 40-60kg = 2 capsules of Decitabine. DEC capsules are ingested ~60 minutes after THU capsules. Weight 61-80kg = 3 capsules of DEC. DEC capsules are ingested ~60 minutes after THU capsules. Weight 81-100kg or higher = 4 capsules of DEC. DEC capsules are ingested ~60 minutes after THU capsules.
Timing between THU and Dec, Frequency of administration: Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days. Treatment on protocol monitoring continues for 52 weeks, however, subjects will have the option to continue beyond this period if it judged to be in their interests.
| Study group | Role | What they receive |
|---|---|---|
| Decitabine + Tetrahydrouridine | Experimental | Tetrahydrouridine (THU) is supplied as 250 mg/capsule, Decitabine (Dec) as 5 mg/capsule. Receives: Drug: Tetrahydrouridine; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNMT1 protein level decreases with an effect size of 1
Differences will be calculated using a paired t-test and alpha=0.05. The effect size is defined as the difference in mean DNMT1-protein levels between post-treatment and pre-treatment divided by the standard deviation and is thus a metric of change in the natural units of the distribution, its standard deviation. Our goal is thus to detect drops in DNMT1 of at least one standard deviation.
Measured: up to 12 months
Secondary outcomes (6)
Clinical Response as measured by RECIST 1.1 guidelines
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: up to 12 months
Best Overall Response
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Measured: up to 12 months
Duration of Response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
Measured: up to 12 months
Duration of stable disease
Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.
Measured: up to 12 months
Overall Survival
Overall Survival will be calculated as time in days from enrollment (signing of the informed consent) to death.
Measured: up to 12 months
Progression-Free Survival
Progression-free Survival will be calculated as time in days from enrollment (signing of the informed consent) to the earlier of:
- Death, or
- Disease progression, by clinical or imaging parameters.
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study start20 Dec 2016
- Primary completion25 Oct 2017
- Study completion30 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yogen Saunthararajah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yogen Saunthararajah, Case Comprehensive Cancer Center
- Investigators
- Devendra P Sohal, MD, MPH, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02847000
- Sponsor's protocol ID
- CASE2216
- Status last verified
- Jan 2019
- First submitted
- 25 Jul 2016
- Last updated
- 9 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Advanced Pancreatic Cancer That Has Progressed Through One or More Lines of Therapy
- ClinicalTrials.gov ID
- NCT02847000
- Acronym / sponsor ID
- CASE2216
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Keywords
- Decitabine, Tetrahydrouridine, Epigenetic Therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Yogen SaunthararajahUniversity, hospital or other
- Study start
- 20 Dec 2016 (actual)
- Primary completion
- 25 Oct 2017 (actual)
- Study completion
- 30 Oct 2017 (actual)
- First posted
- 27 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with pancreatic cancer which has stopped responding to one or more chemotherapy drugs are asked to take part in this study. The study hopes to find out whether decitabine, the drug being studied, will have an effect on pancreatic cancer. The decitabine is being given at a lower dose than its approved use. It is also being given with another drug, tetrahydrouridine (THU), to improve the exposure of your pancreatic cancer cells to decitabine.
The purpose of this study is to determine if the drug combination of decitabine and tetrahydrouridine can recognize a certain DNA target in your cancer. All cells have DNA within them, and tumor cells have abnormal DNA.
Detailed description
Primary Objective The primary goal of this pilot study is to detect decitabine therapy induced DNMT1 protein level decreases with an effect size of 1 using a paired t-test and alpha=0.05. The effect size is defined as the difference in mean DNMT1-protein levels between post-treatment and pre-treatment divided by the standard deviation and is thus a metric of change in the natural units of the distribution, its standard deviation. Our goal is thus to detect drops in DNMT1 of at least one standard deviation.
Secondary Objectives Secondary goals include correlating DNMT1 decreases with clinical response (measured by Response Evaluation Criteria in Solid Tumors [RECIST1.1]), using logistic regression; time to relapse, using a Cox model; tolerability and safety assessment by toxicity characterization using CTCAEv4.
Study Design Single-arm, open-label, proof-of-concept clinical trial in patients with metastatic pancreatic cancer that has progressed on one or more lines of systemic therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine + Tetrahydrouridine | Experimental | Drug: Tetrahydrouridine, Drug: DecitabineTetrahydrouridine (THU) is supplied as 250 mg/capsule, Decitabine (Dec) as 5 mg/capsule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically proven pancreatic carcinoma or adenocarcinoma. Histologies other than carcinoma/adenocarcinoma will not be eligible.
- Subjects must have received one or more prior systemic therapies for this disease, with disease progression or intolerable toxicity precluding further therapy with prior regimen(s).
- Measurable disease per RECIST 1.1.
- ECOG performance status 0 - 2
- Adequate organ function as defined by the following criteria:
Key exclusion criteria (5 listed)
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with oral THU-Dec. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
- Pregnancy or breastfeeding (pregnant or breastfeeding women are excluded from this study because oral THU-Dec has 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 oral THU-Dec, breastfeeding should be discontinued if the mother is treated with oral THU-Dec.
- 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.
- Receiving other investigational agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TetrahydrouridineAlso: THUStarting dose is by weight: THU is supplied as 250 mg/capsule Weight 40-60kg = 2 capsules of Tetrahydrouridine. Weight 61-80kg = 3 capsules of THU. Weight 81-100kg or higher = 4 capsules of THU. Timing between THU and Dec, Frequency of administration: Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days. Treatment on protocol monitoring continues for 52 weeks, however, subjects will have the option to continue beyond this period if it judged to be in their interests. | Drug | Decitabine + Tetrahydrouridine |
| DecitabineAlso: DECStarting dose is by weight: DEC is supplied as 5 mg/capsule. Weight 40-60kg = 2 capsules of Decitabine. DEC capsules are ingested ~60 minutes after THU capsules. Weight 61-80kg = 3 capsules of DEC. DEC capsules are ingested ~60 minutes after THU capsules. Weight 81-100kg or higher = 4 capsules of DEC. DEC capsules are ingested ~60 minutes after THU capsules. Timing between THU and Dec, Frequency of administration: Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days. Treatment on protocol monitoring continues for 52 weeks, however, subjects will have the option to continue beyond this period if it judged to be in their interests. | Drug | Decitabine + Tetrahydrouridine |
Primary outcome
DNMT1 protein level decreases with an effect size of 1
Time frame: up to 12 months
Differences will be calculated using a paired t-test and alpha=0.05. The effect size is defined as the difference in mean DNMT1-protein levels between post-treatment and pre-treatment divided by the standard deviation and is thus a metric of change in the natural units of the distribution, its standard deviation. Our goal is thus to detect drops in DNMT1 of at least one standard deviation.
6 secondary outcomes
Clinical Response as measured by RECIST 1.1 guidelines
Time frame: up to 12 months
Best Overall Response
Time frame: up to 12 months
Duration of Response
Time frame: up to 12 months
Duration of stable disease
Time frame: up to 12 months
Overall Survival
Time frame: up to 12 months
Progression-Free Survival
Time frame: up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Devendra P Sohal, MD, MPH principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tetrahydrouridine and Decitabine in people with Metastatic Pancreatic Adenocarcinoma, run by Yogen Saunthararajah at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNMT1 protein level decreases with an effect size of 1 (time frame: up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.