Rectal CancerPhase 1/2NCT00575640
Hydralazine as a Demethylating Agent in Rectal Cancer
A Phase 1/2 study testing Hydralazine in people with Rectal Cancer, run by University of Arkansas.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Hydralazine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2004to May 2008
- Phase
- Phase 1/2
- 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
- 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:
- Operable rectal cancer (the overwhelming majority are Adenocarcinoma)
- Signed informed consent
- Baseline blood pressure OFF anti-hypertensives over 100/50 mmHg
Who cannot join
- 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
Show all 9Show fewer
- 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.
About this study
Clinically feasible dose of Hydralazine for ~ 3 months, by virtue of its demethylating effect, will:
- Result in re-expression of epigenetically silenced TSGs in rectal cancer specimens.
- Decrease the global methylation in primary cancer cells compared to pre-treatment
Read the detailed description
This study will be conducted as a phase I/II clinical trial. In addition to determining the maximum tolerated dose (MTD) of hydralazine, the phase I trial will be performed to identify unexpected toxicities that may occur when hydralazine is used in conjunction with neoadjuvant chemotherapy in normotensive patients with rectal cancer. Once the phase I trial is successfully completed, the phase II trial to evaluate the efficacy of hydralazine in producing a demethylation effect will begin.
This phase I/II trial will require between 31 to 47 patients to complete.
- Phase I Study
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
- Conditions
- Rectal Cancer
- Being tested
- Hydralazine
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydralazineDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Hydralazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2007 (estimated)
- Study startNov 2004
- Primary completionMay 2008
Why it stopped: No enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- 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
- Phase 1/2
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Investigators
- Ahmed M Safar, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00575640
- Sponsor's protocol ID
- 2004-03
- Status last verified
- Mar 2015
- First submitted
- 14 Dec 2007
- Last updated
- 4 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydralazine as a Demethylating Agent in Rectal Cancer
- ClinicalTrials.gov ID
- NCT00575640
- Acronym / sponsor ID
- 2004-03
- Conditions
- Rectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Nov 2004
- Primary completion
- May 2008 (actual)
- First posted
- 18 Dec 2007 (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.
Clinically feasible dose of Hydralazine for ~ 3 months, by virtue of its demethylating effect, will:
- Result in re-expression of epigenetically silenced TSGs in rectal cancer specimens.
- Decrease the global methylation in primary cancer cells compared to pre-treatment
Detailed description
This study will be conducted as a phase I/II clinical trial. In addition to determining the maximum tolerated dose (MTD) of hydralazine, the phase I trial will be performed to identify unexpected toxicities that may occur when hydralazine is used in conjunction with neoadjuvant chemotherapy in normotensive patients with rectal cancer. Once the phase I trial is successfully completed, the phase II trial to evaluate the efficacy of hydralazine in producing a demethylation effect will begin.
This phase I/II trial will require between 31 to 47 patients to complete.
- Phase I Study
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
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: HydralazineThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- Operable rectal cancer (the overwhelming majority are Adenocarcinoma)
- Signed informed consent
- Baseline blood pressure OFF anti-hypertensives over 100/50 mmHg
Key exclusion criteria (9 listed)
- 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:
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 |
|---|---|---|
| HydralazineDose 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 | 1 |
Primary outcome
The study design calls for an initial phase of dose-escalation in cohorts of 3 patients. There are no intra-patient changes in dose.
1 secondary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2015.
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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.
Ahmed M Safar, MD principal investigator
University of Arkansas
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hydralazine in people with Rectal Cancer, run by University of Arkansas.
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 5 inclusion and 9 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: withdrawn, as of the sponsor's last update on 4 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
The study design calls for an initial phase of dose-escalation in cohorts of 3 patients. There are no intra-patient changes in dose.. 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 4 Mar 2015; AzTrials last refreshed its copy on 6 Nov 2026.