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Sponsored by: |
University of Arkansas |
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Information provided by: | University of Arkansas |
ClinicalTrials.gov Identifier: | NCT00575978 |
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 women with breast 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.
Condition | Intervention | Phase |
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Breast Cancer |
Drug: Hydralazine |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Health Services Research, Open Label, Single Group Assignment, Efficacy Study |
Official Title: | Hydralazine as Demethylating Agent in Breast Cancer |
Estimated Enrollment: | 24 |
Study Start Date: | June 2004 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Hydralazine: Experimental
The objective of this study is to determine the MTD for hydrazaline added to standard neoadjuvant chemotherapy for operable breast cancer. Four dose levels of hydrazalline 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
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
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The objective of this study is to determine the MTD for hydrazaline added to standard neoadjuvant chemotherapy for operable breast cancer. Four dose levels of hydrazalline 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
Patients will be treated in cohorts of 3 and no patient may be treated at more that one dose level. Additional cohorts may not be initiated until toxicity has been fully evaluated in the current cohort of patients. The MTD is exceeded when a dose level produces a dose limiting toxicity (DLT) in at least two of the three patients in a cohort. Dose escalation will proceed by increasing the dose according to the following table.
Number of Events/Number in Cohort Action 0/3 Proceed to next dose level 1/3 Accrue 3 more patients at the same dose 1/3 + 0/3 Proceed to next dose level 1/3 + 1/3 Stop: Previous dose level is MTD 1/3 + 2/3 Stop: Previous dose level is MTD 1/3 + 3/3 Stop: Previous dose level is MTD 2/3 Stop: Previous dose level is MTD 3/3 Stop: Previous dose level is MTD
If the MTD has been exceeded by dose escalation and only one cohort with no observed toxicities was tested at the previous dose level, an additional cohort of 3 patients will be tested at the previous dose level. Thus, six patients must be treated at the dose declared the MTD. In the unlikely event that 150 mg/day of hydralazine, the starting dose, produces two or more DLTs, the daily dose of hydralazine will be reduced by 50mg to100 mg/day. If two or more toxicities are observed at this reduced dose level, the study will be stopped and the phase II study will not be performed.
This phase I study will require between 9 to 24 patients. The cohort of six patients treated at the MTD will be used in the subsequent phase II trial.
Definition of Dose Limiting Toxicities
Because the study drug is not a cytotoxic agent, is being "added" to a toxic chemotherapy regimen in women likely to be normotensive, and because the drug has been evaluated in the cardiovascular literature with maximum clinical doses at 300 mg/d, we made the following decisions that deviate from classic "cytotoxic" agent schemes. The deviations are as follows:
The definition of a DLT will not adhere to the NCI CTC - designed for cytotoxic agents, but will rather be simply the tolerability of the drug by the patient as documented in the protocol and reproduced below:
Patients having to go off the drug will be considered as DLT events.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients referred to the breast cancer service for diagnostic evaluation for "breast growth" will be candidates to participate in this study. Patients with history of elevated blood pressure and who are already on anti-hypertensives would be ideal candidates for this project. In such situation, hydralazine will replace other anti-hypertensives. There is no age limit for this study. Inclusion criteria are as follows:
Exclusion Criteria:
Responsible Party: | University of Arkansas for Medical Sciences ( Ahmed Safar, MD ) |
Study ID Numbers: | 2003-23 |
Study First Received: | December 14, 2007 |
Last Updated: | December 3, 2008 |
ClinicalTrials.gov Identifier: | NCT00575978 |
Health Authority: | United States: Institutional Review Board |
breast cancer |
Skin Diseases Hydralazine Breast Neoplasms Breast Diseases |
Vasodilator Agents Neoplasms Neoplasms by Site Therapeutic Uses |
Cardiovascular Agents Antihypertensive Agents Pharmacologic Actions |