Hydralazine as a Demethylating Agent in Rectal Cancer

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Clinically feasible dose of Hydralazine for ~ 3 months, by virtue of its demethylating effect, will:

1. Result in re-expression of epigenetically silenced TSGs in rectal cancer specimens.

2. Decrease the global methylation in primary cancer cells compared to pre-treatment

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Arkansas
• Treatments: Hydralazine

Criteria

Inclusion Criteria:

The principal objective of this study is to perform a molecular evaluation for the reversal of methylation in clinical material collected at two different time points. The first sample representing untreated (the biopsy sample), and later a hydralazine-treated specimen (the resection specimen). Accordingly, we are not using routine inclusion criterion for enrollment (such as histology or clinical stage), but realize that the majority of operable rectal cancers will be stages II-III, and that treatment-again not specified or restricted-will very likely follow the standard therapy for this disease (infusional 5-Fluorouracil and radiation therapy). The accrual target at the phase II segment of this trial is small and that does not allow for any traditional clinical endpoints assessment (such as response rate, time to treatment failure or survival). Accordingly, we do not plan on following these endpoint as part of this study.

Patients referred to the surgery or gastroenterology services for diagnostic evaluation for rectal cancer will be candidates to participate in this study. Patients with history of elevated blood pressure and who are already on anti-hypertensive drugs would be ideal candidates for this project. In such situation, hydralazine will replace other anti-hypertensives for the duration of study only. There is no age limit for this study. Inclusion criteria are as follows:

1. Operable rectal cancer (the overwhelming majority are Adenocarcinoma)

2. Signed informed consent

3. Baseline blood pressure OFF anti-hypertensives over 100/50 mmHg

Exclusion Criteria:

1. Pre-existing hypotension (as defined in this protocol BP 100/50)

2. Pre-existing liver disease (liver function tests over 2x upper limits of normal ULM).

3. Pre-existing kidney (serum creatinine over 2 mg/dl).

4. Medical necessity to remain on beta-blockers that cannot be met by other agents.

5. Coronary even in the preceding 2 months prior to enrollment. Coronary evens include any of the following:

• Acute Myocardial Infarction

• Cardiac catheterization regardless of outcome of procedure or need of intervention

• History of Valvular heart disease

• History of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction.