NCT02847000

p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Pancreatic Cancer

p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Advanced Pancreatic Cancer That Has Progressed Through One or More Lines of Therapy

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Yogen Saunthararajah · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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.

Conditions

• Metastatic Pancreatic Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Tetrahydrouridine	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.
DRUG	Decitabine	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.

Timeline

• Start date: 2016-12-20
• Primary completion: 2017-10-25
• Completion: 2017-10-30
• First posted: 2016-07-27
• Last updated: 2019-01-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study