Advanced CancersPhase 1NCT00496444
Azacytidine and Valproic Acid in Patients With Advanced Cancers
A Phase 1 study testing Azacitidine and Valproic Acid in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objective: 1. To evaluate side effects and maximum tolerated dose of azacitidine and valproic acid in patients with advanced cancer. Secondary Objectives: 1. To perform a preliminary assessment of the histone acetylation and DNA methylation effects of this combination on peripheral blood mononuclear cells… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Advanced Cancers
- What is being tested?
- Azacitidine and Valproic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Oct 2009
- Phase
- Phase 1
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with pathologically confirmed malignancy that is metastatic or unresectable and refractory to standard therapy or for whom there is no standard therapy that induces complete remission (CR) of at least 10% or an increased survival of at least 3 months.
- There is no maximum allowable number of prior chemotherapy regimens, provided all other eligibility criteria are met.
- No chemotherapy, radiotherapy, investigational agents or surgery within four weeks.
- ECOG performance status 2 or less.
- Normal organ and marrow function - ANC > 1500/microL - Platelets > 100,000/microL - Total bilirubin < 2.0 mg/dL - Creatinine < 2.0 mg/dL
- The effect of azacytidine on the development of human fetus is unknown. Because of the chemotherapy agents are known to be teratogenic, women and men of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of the study.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Uncontrolled concurrent illness such as neutropenic fever,shock, symptomatic congestive heart failure (NYHA class III or IV).
- Hypersensitivity to divalproex sodium, valproic acid, or valproate sodium
- Known or suspected hypersensitivity to azacitidine or mannitol.
- Nursing and pregnant women.
- Patients with urea cycle disorders (UCD): - History of unexplained coma, encephalopathy, or mental retardation - Encephalopathy associated with a protein load - Pregnancy-related or postpartum encephalopathy - History of elevated plasma ammonia or glutamine - Those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance. - Those with a family history of UCD or unexplained infant deaths (particularly males).
- Patients with a known ornithine transcarbamylase disorder, history of unexplained coma or a family history of ornithine transcarbamylase disorder are excluded from this study.
- Patients younger than 2-year old since valproic acid safety is not proven in this age group.
- Leukemias and MDS are excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I Study of Low-Dose Hypomethylating Agent Azacitidine Combined With the Histone Deacetylase Inhibitor Valproic Acid in Patients With Advanced Cancers
Primary Objective:
- To evaluate side effects and maximum tolerated dose of azacitidine and valproic acid in patients with advanced cancer.
Secondary Objectives:
- To perform a preliminary assessment of the histone acetylation and DNA methylation effects of this combination on peripheral blood mononuclear cells (PBMC).
- To assess the clinical anti-tumor activity (objective response including complete and partial responses) of this combination in patients with advanced cancer, in a descriptive fashion.
Read the detailed description
Azacitidine is a new chemotherapy drug that is designed to destroy cancer cells at high doses. At low doses, it is designed to destroy some cancer cells as well as cause changes that may make cancer cells less harmful. Valproic acid is a drug that is used in every day practice in the treatment of seizures, migraine headache, and mood disturbance in bipolar disorders.
Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete physical exam, including routine blood tests (about 4 teaspoons). You may have to get either a CT scan or a MRI to measure your disease if you have not had one within 1 month. Women who are able to have children must have a negative blood-pregnancy test.
If you are found to be eligible to take part in this study, you will receive the study drug in "cycles." Cycles will generally be 4 weeks long but may be longer, depending on any side effects you experience from the azacitidine. During each cycle, you will receive azacitidine under the skin once each day for the first 10 days (Day 1 to Day 10). You will then have an 18-day break during which you will not receive azacitidine injections for the rest of the cycle. Additionally, you will take valproic acid pills by mouth, every day, starting the first day of the first cycle (Day 1 to Day 28). You will take valproic acid every day while on study without interruption.
The dose of azacitidine that you receive will depend on when you enroll in this study. You will be part of a study group "cohort" (6 patients will be enrolled in each cohort). All members of a cohort receive the same dose of azacitidine when they begin receiving the study drug. Each new cohort will receive a higher dose than the cohort before. The dose of azacitidine that you receive may be adjusted depending on how well you tolerate it. The starting dose of valproic acid is fixed for all the patients, but this dose may be adjusted by your physician based on the results of your blood work.
You will have a physical exam and blood tests (about 1 tablespoon each) every two weeks of the first two study drug cycles. For further cycles, you will have a physical exam and blood test only once a month. Your disease will be measured by CT scan or MRI after every 2 treatment cycles.
You may continue to receive the study drug on this study until your disease gets worse or intolerable side effects occur. After your participation in this study is over, you will receive follow-up care, as is standard of care for your disease.
This is an investigational study. The FDA has approved azacitidine for a blood disease known as myelodysplastic syndrome. Its use in this study is experimental. The valproic acid is a drug approved by the FDA for treatment of seizure, bipolar disorders, and migraine headaches. Up to 68 patients will take part in the study. All will be enrolled at M. D. Anderson.
- Conditions
- Advanced Cancers
- Being tested
- Azacitidine, Valproic Acid
- Keywords
- Advanced Cancers, Azacytidine, 5-Azacitidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Valproic Acid, Depakene
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5-Azacitidine, 5-aza, Vidaza, 5-AZC
Starting Dose 20 mg/m^2 administered subcutaneously (under the skin), daily, for ten days (Days 1 -10) of every 4 Week Cycle.
Valproic AcidDrug
Also called Depakene
Starting Dose 10 mg/Kg once daily by mouth, every day of 4 Week Cycle.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine + Valproic Acid | Experimental | Not described Receives: Drug: Azacitidine; Drug: Valproic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
To find the highest safe dose of the drug azacitidine that can be given in combination with valproic acid in the treatment of solid tumors.
Measured: 4 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2007 (estimated)
- Study startMay 2005
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancersStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Razelle Kurzrock, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496444
- Sponsor's protocol ID
- 2004-0735
- Status last verified
- Jul 2012
- First submitted
- 2 Jul 2007
- Last updated
- 1 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Low-Dose Hypomethylating Agent Azacitidine Combined With the Histone Deacetylase Inhibitor Valproic Acid in Patients With Advanced Cancers
- ClinicalTrials.gov ID
- NCT00496444
- Acronym / sponsor ID
- 2004-0735
- Conditions
- Advanced Cancers
- Keywords
- Advanced Cancers, Azacytidine, 5-Azacitidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- May 2005
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 4 Jul 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.
Primary Objective:
- To evaluate side effects and maximum tolerated dose of azacitidine and valproic acid in patients with advanced cancer.
Secondary Objectives:
- To perform a preliminary assessment of the histone acetylation and DNA methylation effects of this combination on peripheral blood mononuclear cells (PBMC).
- To assess the clinical anti-tumor activity (objective response including complete and partial responses) of this combination in patients with advanced cancer, in a descriptive fashion.
Detailed description
Azacitidine is a new chemotherapy drug that is designed to destroy cancer cells at high doses. At low doses, it is designed to destroy some cancer cells as well as cause changes that may make cancer cells less harmful. Valproic acid is a drug that is used in every day practice in the treatment of seizures, migraine headache, and mood disturbance in bipolar disorders.
Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete physical exam, including routine blood tests (about 4 teaspoons). You may have to get either a CT scan or a MRI to measure your disease if you have not had one within 1 month. Women who are able to have children must have a negative blood-pregnancy test.
If you are found to be eligible to take part in this study, you will receive the study drug in "cycles." Cycles will generally be 4 weeks long but may be longer, depending on any side effects you experience from the azacitidine. During each cycle, you will receive azacitidine under the skin once each day for the first 10 days (Day 1 to Day 10). You will then have an 18-day break during which you will not receive azacitidine injections for the rest of the cycle. Additionally, you will take valproic acid pills by mouth, every day, starting the first day of the first cycle (Day 1 to Day 28). You will take valproic acid every day while on study without interruption.
The dose of azacitidine that you receive will depend on when you enroll in this study. You will be part of a study group "cohort" (6 patients will be enrolled in each cohort). All members of a cohort receive the same dose of azacitidine when they begin receiving the study drug. Each new cohort will receive a higher dose than the cohort before. The dose of azacitidine that you receive may be adjusted depending on how well you tolerate it. The starting dose of valproic acid is fixed for all the patients, but this dose may be adjusted by your physician based on the results of your blood work.
You will have a physical exam and blood tests (about 1 tablespoon each) every two weeks of the first two study drug cycles. For further cycles, you will have a physical exam and blood test only once a month. Your disease will be measured by CT scan or MRI after every 2 treatment cycles.
You may continue to receive the study drug on this study until your disease gets worse or intolerable side effects occur. After your participation in this study is over, you will receive follow-up care, as is standard of care for your disease.
This is an investigational study. The FDA has approved azacitidine for a blood disease known as myelodysplastic syndrome. Its use in this study is experimental. The valproic acid is a drug approved by the FDA for treatment of seizure, bipolar disorders, and migraine headaches. Up to 68 patients will take part in the study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine + Valproic Acid | Experimental | Drug: Azacitidine, Drug: Valproic Acid |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with pathologically confirmed malignancy that is metastatic or unresectable and refractory to standard therapy or for whom there is no standard therapy that induces complete remission (CR) of at least 10% or an increased survival of at least 3 months.
- There is no maximum allowable number of prior chemotherapy regimens, provided all other eligibility criteria are met.
- No chemotherapy, radiotherapy, investigational agents or surgery within four weeks.
- ECOG performance status 2 or less.
- Normal organ and marrow function - ANC > 1500/microL - Platelets > 100,000/microL - Total bilirubin < 2.0 mg/dL - Creatinine < 2.0 mg/dL
Key exclusion criteria (8 listed)
- Uncontrolled concurrent illness such as neutropenic fever,shock, symptomatic congestive heart failure (NYHA class III or IV).
- Hypersensitivity to divalproex sodium, valproic acid, or valproate sodium
- Known or suspected hypersensitivity to azacitidine or mannitol.
- Nursing and pregnant women.
- Patients with urea cycle disorders (UCD): - History of unexplained coma, encephalopathy, or mental retardation - Encephalopathy associated with a protein load - Pregnancy-related or postpartum encephalopathy - History of elevated plasma ammonia or glutamine - Those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance. - Those with a family history of UCD or unexplained infant deaths (particularly males).
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 |
|---|---|---|
| AzacitidineAlso: 5-Azacitidine, 5-aza, Vidaza, 5-AZCStarting Dose 20 mg/m^2 administered subcutaneously (under the skin), daily, for ten days (Days 1 -10) of every 4 Week Cycle. | Drug | Azacitidine + Valproic Acid |
| Valproic AcidAlso: DepakeneStarting Dose 10 mg/Kg once daily by mouth, every day of 4 Week Cycle. | Drug | Azacitidine + Valproic Acid |
Primary outcome
To find the highest safe dose of the drug azacitidine that can be given in combination with valproic acid in the treatment of solid tumors.
Time frame: 4 Years
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 1 Aug 2012.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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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.
Razelle Kurzrock, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine and Valproic Acid in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.
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 7 inclusion and 8 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 1 Aug 2012. 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 United States. 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 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.
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?
To find the highest safe dose of the drug azacitidine that can be given in combination with valproic acid in the treatment of solid tumors. (time frame: 4 Years). 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 1 Aug 2012.