Refractory Solid TumorsPhase 2NCT00404508
A Phase II Study of Epigenetic Therapy to Overcome Chemotherapy Resistance in Refractory Solid Tumors
A Phase 2 study testing Hydralazine and magnesium valproate in people with Refractory Solid Tumors, run by National Institute of Cancerología at 1 site in Mexico.
Trial summary
Chemotherapy resistance, either innate or acquired requires for its development, expression changes on a large number of genes therefore, it has been hypothesized that epigenetic-mediated changes could be the responsible driving force for chemotherapy resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Solid Tumors
- What is being tested?
- Hydralazine and magnesium valproate
- How many people
- 15 participants
- Where
- 1 siteMexico
- Study dates
- Sep 2005to Oct 2006
- Phase
- Phase 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
- Aged18 years and older.
- Histologically proven malignant solid tumors who were receiving their second, third or fourth line of palliative chemotherapy and who showed at the second or third course progressive disease as their maximum response according to the RECIST criteria or to the IGCG CA125 criteria in case of ovarian cancer patients.
- Measurable disease defined by 1 of the following criteria: Any unidimensional measurable lesion ≥ 10 mm by standard MRI or CT scan for solid tumors; or at least 1 non-measurable lesion that is evaluable by nuclear medicine, tumor markers, or other reliable measures.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2; Absolute leukocyte count (≥4000/mm3), platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL; total bilirubin, aspartate amino transferase (AST) and alanine amino transferase (ALT) <1.5 the upper normal limit (UNL), creatinine ≤1.2 mg/dL or a calculated creatinine clearance of ≥60 mL/min.
- Life expectancy of more than three months,
- Written informed consent.
Who cannot join
- History of allergy to hydralazine or valproate.
- Past or present condition of rheumatic disease, central nervous system disease, heart failure from aortic stenosis and postural hypotension as diagnosed by a physician.
- Previous use of the experimental drugs (hydralazine and magnesium valproate)
- Pregnancy or breast-feeding.
- Uncontrolled systemic disease or infection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Epigenetic Therapy With Hydralazine and Magnesium Valproate to Overcome Chemotherapy Resistance in Refractory Solid Tumors
Chemotherapy resistance, either innate or acquired requires for its development, expression changes on a large number of genes therefore, it has been hypothesized that epigenetic-mediated changes could be the responsible driving force for chemotherapy resistance. Aberrant DNA methylation and histone deacetylation are the main epigenetic alterations hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) may overcome resistance in refractory solid tumors.
Patients will be treated with hydralazine and magnesium valproate starting from day -7 until chemotherapy ends which consists on the same pre-study protocol regimen on which patients progressed. Response and toxicity were evaluated. Global DNA methylation and HDAC activity were evaluated in the peripheral blood cells, as well as the plasma levels of valproic acid and hydralazine.
Read the detailed description
Eligible patients after signing informed consent will undergo study evaluation and acetylation status typing before being treated. Patients will begin treatment (day -7) with a daily dose of a slow-release formulation of hydralazine tablets containing either 182 mg for rapid-acetylators or 83 mg for slow-acetylators and slow-release tablets containing 700mg of magnesium valproate at a dose of 40mg/Kb t.i.d. Both hydralazine and magnesium valproate will be administered from day -7 until the last day of the last chemotherapy cycle. Chemotherapy will initiate at day 1 (after seven days of being taken hydralazine and magnesium valproate) with the same pre-study protocol regimen at which patients showed tumor progression. Toxicity will be evaluated after each course of chemotherapy. Response will be evaluated at the third course of chemotherapy. Promoter of selected genes will be evaluated by methylation-specific PCR in serum DNA before and after 7 days of treatment with hydralazine and valproate.
- Conditions
- Refractory Solid Tumors
- Being tested
- Hydralazine and magnesium valproate
- Keywords
- Hydralazine, Magnesium Valproate, Chemotherapy resistance, Epigenetic therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydralazine and magnesium valproateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical benefit (complete response, partial response and stable disease)
Safety
Secondary outcomes (3)
Global DNA methylation
HDAC inhibition
Gene promoter demethylation from serum DNA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2006 (estimated)
- Study startSep 2005
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory Solid TumorsStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Cancerología
- Sponsor type
- Other government
- Collaborators
- Psicofarma, S.A. De C.V., National Council of Science and Technology, Mexico
- Investigators
- Alfonso Duenas-Gonzalez, MD PhD, Study director, National Institute of Cancerologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00404508
- Sponsor's protocol ID
- 005/32/DII
- Status last verified
- Nov 2006
- First submitted
- 25 Nov 2006
- Last updated
- 28 Nov 2006
- Results posted
- No
Publications
Candelaria M, Gallardo-Rincon D, Arce C, Cetina L, Aguilar-Ponce JL, Arrieta O, Gonzalez-Fierro A, Chavez-Blanco A, de la Cruz-Hernandez E, Camargo MF, Trejo-Becerril C, Perez-Cardenas E, Perez-Plasencia C, Taja-Chayeb L, Wegman-Ostrosky T, Revilla-Vazquez A, Duenas-Gonzalez A. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann Oncol. 2007 Sep;18(9):1529-38. doi: 10.1093/annonc/mdm204.
PubMed 17761710
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Epigenetic Therapy With Hydralazine and Magnesium Valproate to Overcome Chemotherapy Resistance in Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00404508
- Acronym / sponsor ID
- 005/32/DII
- Conditions
- Refractory Solid Tumors
- Keywords
- Hydralazine, Magnesium Valproate, Chemotherapy resistance, Epigenetic therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants
- Lead sponsor
- National Institute of CancerologíaOther government
- Collaborators
- Psicofarma, S.A. De C.V., National Council of Science and Technology, Mexico
- Study start
- Sep 2005
- Study completion
- Oct 2006
- First posted
- 28 Nov 2006 (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.
Chemotherapy resistance, either innate or acquired requires for its development, expression changes on a large number of genes therefore, it has been hypothesized that epigenetic-mediated changes could be the responsible driving force for chemotherapy resistance. Aberrant DNA methylation and histone deacetylation are the main epigenetic alterations hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) may overcome resistance in refractory solid tumors.
Patients will be treated with hydralazine and magnesium valproate starting from day -7 until chemotherapy ends which consists on the same pre-study protocol regimen on which patients progressed. Response and toxicity were evaluated. Global DNA methylation and HDAC activity were evaluated in the peripheral blood cells, as well as the plasma levels of valproic acid and hydralazine.
Detailed description
Eligible patients after signing informed consent will undergo study evaluation and acetylation status typing before being treated. Patients will begin treatment (day -7) with a daily dose of a slow-release formulation of hydralazine tablets containing either 182 mg for rapid-acetylators or 83 mg for slow-acetylators and slow-release tablets containing 700mg of magnesium valproate at a dose of 40mg/Kb t.i.d. Both hydralazine and magnesium valproate will be administered from day -7 until the last day of the last chemotherapy cycle. Chemotherapy will initiate at day 1 (after seven days of being taken hydralazine and magnesium valproate) with the same pre-study protocol regimen at which patients showed tumor progression. Toxicity will be evaluated after each course of chemotherapy. Response will be evaluated at the third course of chemotherapy. Promoter of selected genes will be evaluated by methylation-specific PCR in serum DNA before and after 7 days of treatment with hydralazine and valproate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged18 years and older.
- Histologically proven malignant solid tumors who were receiving their second, third or fourth line of palliative chemotherapy and who showed at the second or third course progressive disease as their maximum response according to the RECIST criteria or to the IGCG CA125 criteria in case of ovarian cancer patients.
- Measurable disease defined by 1 of the following criteria: Any unidimensional measurable lesion ≥ 10 mm by standard MRI or CT scan for solid tumors; or at least 1 non-measurable lesion that is evaluable by nuclear medicine, tumor markers, or other reliable measures.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2; Absolute leukocyte count (≥4000/mm3), platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL; total bilirubin, aspartate amino transferase (AST) and alanine amino transferase (ALT) <1.5 the upper normal limit (UNL), creatinine ≤1.2 mg/dL or a calculated creatinine clearance of ≥60 mL/min.
- Life expectancy of more than three months,
Key exclusion criteria (5 listed)
- History of allergy to hydralazine or valproate.
- Past or present condition of rheumatic disease, central nervous system disease, heart failure from aortic stenosis and postural hypotension as diagnosed by a physician.
- Previous use of the experimental drugs (hydralazine and magnesium valproate)
- Pregnancy or breast-feeding.
- Uncontrolled systemic disease or infection.
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 |
|---|---|---|
| Hydralazine and magnesium valproate | Drug | – |
Primary outcome
Clinical benefit (complete response, partial response and stable disease)
Safety
3 secondary outcomes
Global DNA methylation
HDAC inhibition
Gene promoter demethylation from serum DNA
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2006.
- Derived from this study: PubMed 17761710Candelaria M, Gallardo-Rincon D, Arce C, Cetina L, Aguilar-Ponce JL, Arrieta O, Gonzalez-Fierro A, Chavez-Blanco A, de la Cruz-Hernandez E, Camargo MF, Trejo-Becerril C, Perez-Cardenas E, Perez-Plasencia C, Taja-Chayeb L, Wegman-Ostrosky T, Revilla-Vazquez A, Duenas-Gonzalez A. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann Oncol. 2007 Sep;18(9):1529-38. doi: 10.1093/annonc/mdm204.
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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.
Alfonso Duenas-Gonzalez, MD PhD study director
National Institute of Cancerologia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydralazine and magnesium valproate in people with Refractory Solid Tumors, run by National Institute of Cancerología at 1 site in Mexico.
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 6 inclusion and 5 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: finished, as of the sponsor's last update on 28 Nov 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical benefit (complete response, partial response and stable disease). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00404508, which also lists 1 linked publication.
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 28 Nov 2006.