Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antihypertensive Agents

Vasodilator Agents

All Drugs and Chemicals

Hydralazine

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

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

Ahmed M Safar, MD

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

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

Hydralazine as a Demethylating Agent in Rectal Cancer

University of Arkansas

Ahmed M. Safar, MD

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Cisplatin

Valproic Acid

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Neurotransmitter Agents

Hydralazine and magnesium valproate

Punch biopsy of the primary tumor

Alfonso Duenas-Gonzalez, MD, PhD.

The current standard for locally advanced cervical cancer is concurrent cisplatin-based chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the radiation and chemotherapy effects.

Objective. To determine response rate, safety and biological effects of hydralazine and magnesium valproate when added to cisplatin chemoradiation.

Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase the clinical complete response rate to 95% as compared to 75% as seen in historical controls treated with cisplatin chemoradiation in FIGO stage IIIB patients.

Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical carcinoma with no previous treatment will be included. Patients will be typed for acetylator status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at 40mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy). Clinical response rate, safety and transcriptome changes will be analyzed.

Eligible patients after signing informed consent will undergo study evaluation and then typed for acetylator phenotype before receive either 182 or 83 mg of hydralazine, and magnesium valproate at 30mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy. External beam radiation will be delivered by megavoltage equipment for a dose of 50gy (2Gy fraction from monday to friday) concurrently with cisplatin at 40mg/m2 for six weeks. Within one to two weeks, intracavitary brachytherapy (low-dose rate, Cesium sources) will be delivered to achieve at least 85Gy to point A. A punch biopsy from the primary tumor will be taken at entering the study and at day 8 of hydralazine and valproate treatment (before the first dose of cisplatin and radiation)to assess global gene expression profiling by microarray analysis. Blood samples will be taken to assess global DNA methylation, histone deacetylase activity and plasma levels of hydralazine and valproic acid.

Clinical response and toxicity will be assessed.

Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer

A Phase II Study of Transcriptional Therapy With the DNA Demethylating Hydralazine and the HDAC Inhibitor Valproate Associated to Concomitant Cisplatin Chemoradiation in FIGO Stage III Cervical Cancer.

National Council of Science and Technology, Mexico

Psicofarma S.A. de C.V.

National Institute of Cancerología

Symptoms and General Pathology

Recurrence

Topotecan

Cisplatin + Topotecan plus hydralazine valproate

Placebo

Alfonso Dueñas-Gonzalez, MD PhD

Lucely Cetina, MD

Myrna Candelaria, MD

The current standard for recurrent, persistent or metastatic cervical cancer is palliative chemotherapy with cisplatin topotecan, however, the results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the cytotoxicity of chemotherapy.

Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate plus standard cisplatin topotecan against placebo plus cisplatin topotecan upon progression-free survival.

Hypothesis. Hydralazine and magnesium valproate associated to cisplatin topotecan will increase progression-free survival from 4.6 to 7.6 months as compared with the same regimen of chemotherapy plus placebo.

Randomized, double-blind phase III trial. A total of 143 patients (alpha 0.5, power 0.8)with metastatic, persistent or recurrent cervical cancer without previous systemic treatment will be randomized to cisplatin topotecan + placebo or cisplatin topotecan hydralazine valproate for 6 courses every 3 weeks. Patients will receive an oral dose of hydralazine of 182mg (rapid) or 83mg (slow) according to the acetylator phenotype in a single daily dose and magnesium valproate at an oral dose of 40mg/Kg t.i.d. Both drugs in a slow-release formulation. Experimental drugs or placebo will start from seven days before day 1 of chemotherapy until the end of the sixth course.

Hydralazine Valproate for Cervical Cancer

Randomized, Double-Blind, Phase III Trial of Chemotherapy Plus the Transcriptional Therapy Hydralazine and Magnesium Valproate Versus Chemotherapy Plus Placebo in Recurrent and Metastatic Cervical Cancer.

Lucely Cetina

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

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

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.

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:

* Dose escalation beyond the "CLINNICALLY MAXIMAL" dose of 250 mg/d are not planned, and
* 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:

  1. Symptomatic hypotension,
  2. Blood pressure recording of \< 90 mmHg systolic, or \<55 mgHg diastolic,
  3. Other side effects deemed unacceptable either to the patient or the treating physician, and
  4. Patient request/refusal to continue on study.

Patients having to go off the drug will be considered as DLT events.

Hydralazine as Demethylating Agent in Breast Cancer

Ahmed Safar, MD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hydralazine as a Demethylating Agent in Rectal Cancer	NCT00575640	Rectal Cancer	Hydralazine	18 Years -	University of Arkansas
Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer	NCT00404326	Cervical Cancer	Hydralazine and... Punch biopsy of...	18 Years - 70 Years	National Institute of Cancerología
Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer	NCT00404326	Cervical Cancer	Hydralazine and... Punch biopsy of...	18 Years - 70 Years	National Institute of Cancerología
Hydralazine Valproate for Cervical Cancer	NCT00532818	Metastatic Cerv...	Hydralazine and... Placebo	18 Years -	National Institute of Cancerología
Hydralazine as Demethylating Agent in Breast Cancer	NCT00575978	Breast Cancer	Hydralazine	18 Years -	University of Arkansas
Hydralazine as a Demethylating Agent in Rectal Cancer	NCT00575640	Rectal Cancer	Hydralazine	18 Years -	University of Arkansas
Hydralazine Valproate for Cervical Cancer	NCT00532818	Metastatic Cerv...	Hydralazine and... Placebo	18 Years -	National Institute of Cancerología

Spots Global Cancer Trial Database for hydralazine

Every month we try and update this database with for hydralazine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hydralazine

Every month we try and update this database with for hydralazine cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hydralazine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.