Hydralazine as a Demethylating Agent in Rectal Cancer

NCT00575640 | Withdrawn Phase 1

• 1 other identifier: 2004-03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

1. 1.Result in re-expression of epigenetically silenced TSGs in rectal cancer specimens.
2. 2.Decrease the global methylation in primary cancer cells compared to pre-treatment

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• The study design calls for an initial phase of dose-escalation in cohorts of 3 patients. There are no intra-patient changes in dose.

Secondary Outcomes (1)

• Subsequent to this Phase I scheme, the study will continue with the selected dose-level (on toxicity and tolerability grounds) to accrue patients in a phase II scheme.

Study Arms (1)

1

ACTIVE COMPARATOR

The objective of this study is to determine the MTD for Hydralazine added to standard neoadjuvant chemotherapy for operable recta cancer. Four dose levels of hydralazine are planned: Dose Level 1: 150 mg/d 50 mg PO TID Dose Level 2: 200 mg/d 50 mg PO QID Dose Level 3: 225 mg/d 75 mg PO TID

Drug: Hydralazine

Interventions

Hydralazine DRUG

Dose Level 1: 150 mg/d 50 mg PO TID Dose Level 2: 200 mg/d 50 mg PO QID Dose Level 3: 225 mg/d 75 mg PO TID

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Operable rectal cancer (the overwhelming majority are Adenocarcinoma)
• Signed informed consent
• Baseline blood pressure OFF anti-hypertensives over 100/50 mmHg

You may not qualify if:

• Pre-existing hypotension (as defined in this protocol BP 100/50)
• Pre-existing liver disease (liver function tests over 2x upper limits of normal ULM).
• Pre-existing kidney (serum creatinine over 2 mg/dl).
• Medical necessity to remain on beta-blockers that cannot be met by other agents.
• 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.

Sponsors & Collaborators

• University of Arkansas: lead

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Hydralazine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ahmed M Safar, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 18, 2007
• Study Start: November 1, 2004
• Primary Completion: May 1, 2008
• Last Updated: March 4, 2015

Record last verified: 2015-03