Solid TumorsPhase 1NCT00529022
Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer
A Phase 1 study testing Azacitidine, Valproic Acid and Carboplatin in people with Solid Tumors, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find out if giving azacitidine with valproic acid plus carboplatin can help control advanced cancer. The safety of this treatment will be studied as well. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Azacitidine, Valproic Acid and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Oct 2012
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient has histologically or cytologically confirmed diagnosis of advanced solid tumor (that has progressed following standard therapy or for whom, in the opinion of the investigator, no standard effective therapy is available) during the phase I study. Only patients who have platinum resistant epithelial carcinoma of the ovary, fallopian tube or primary peritoneal carcinoma are enrolled onto the phase 2 study, if progresses to phase 2. According to standard Gynecologic Oncology Group (GOG) criteria platinum resistant is defined to have had a disease-free interval of shorter than 6 months following platinum treatment.
- Patient has measurable or evaluable disease by radiological imaging techniques with documented progression within 1 month before study entry or disease that has not responded to treatment. (Pleural effusions, ascites, osseous metastasis, elevation of tumor marker and lesions located in previously irradiated areas are not considered measurable).
- Patient is willing to comply with study procedures to have blood collections for correlative studies.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Patient must be informed of the investigational nature of this study and must sign and give written Internal Review Board (IRB) approved informed consent in accordance with institutional guidelines.
- If patient is of child-bearing potential, she or he has agreed to practice an effective method of birth control during the study and up to 3 months after the last treatment.
- Patient has adequate liver and renal function: serum albumin =/>3.0 g/dL; serum bilirubin =/<2.0 mg/dL; alanine aminotransferase (ALT) =/<3* upper limit of normal (uln); and serum creatinine =/< 2.0 mg/dL or a calculated creatinine clearance of at least 40 ml/min.
- Patient has adequate bone marrow reserve. Absolute neutrophil count (ANC) =/>1,500/ul, Platelet count =/>100,000/ul, and Hemoglobin =/>9.0g/dL.
Who cannot join
- Any concurrent chemotherapy.
- Underlying medical condition that might be aggravated by treatment or that cannot be controlled, such as active uncontrolled serious infection and cardiac dysfunction.
- Medical and psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
- Known hypersensitivity to azacitidine, valproic acid, carboplatin or their analogs.
- Failure to recover from any prior surgery within 4 weeks of study entry.
- Pregnant or lactating.
Show all 12Show fewer
- Any treatment specific for tumor control within 3 weeks of dosing with study drugs (within 2 weeks if given weekly or within 6 weeks for nitrosoureas or mitomycin C) or failure to recover from the toxic effect of any of these therapies prior to study entry. Any investigational drug within 30 days of first day of dosing.
- Any signs of intestinal obstruction interfering with nutrition or oral intake.
- History of central nervous system (CNS) metastasis unless the patient has had surgery or radiation, and does not require oral or intravenous corticosteroids or anticonvulsants.
- Advanced malignant hepatic tumors that are defined as the total hepatic metastases more than 25% of hepatic parenchyma.
- History of high dose chemotherapy for ovarian cancer in phase 2 of the study, if Phase 2 of study needed. High dose chemotherapy is defined as the intensity and/or the density of a chemotherapeutic agent that are beyond standard of care for ovarian cancer treatment.
- History of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, basal cell or squamous cell skin cancer, or other cancer for which the patient has been disease free for at least two years in phase 2 study, if Phase 2 of study needed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer
The goal of this clinical research study is to find out if giving azacitidine with valproic acid plus carboplatin can help control advanced cancer. The safety of this treatment will be studied as well. Researchers will also collect some extra blood samples for molecular marker studies (studies that may help researchers predict how participants respond to the combined therapy).
There were to be two phases of this study: a Phase 1 portion to find acceptable doses of the study drug combination, and a Phase 2 portion to study the response rates to the treatment schedule. The study did not proceed to the Phase 2 portion.
Read the detailed description
The Study Drugs:
Researchers want to see if the combination of azacitidine, carboplatin, and valproic may work better together to control advanced cancer.
- Azacitidine is designed to activate ("turn on") certain genes in cancer cells whose job is to fight tumors, which may also make azacitidine work better with other anti-tumor drugs.
- Carboplatin is designed to block the growth of cancer cells by stopping cell division, which may cause the cells to die.
- Valproic acid is an anti-seizure medication that may also have cancer-fighting abilities. This drug may be able to activate tumor-fighting genes, causing cancer cells to die.
Phase 1 (Dose Escalation) and Phase 2 (Treatment):
Participants will be enrolled on Phase 1 of the study in groups of 3. Each group will receive a different combination of the study drugs. If the first group of 3 tolerates the study drug combination well, the next group of 3 will be enrolled, and their dose(s) of carboplatin and/or valproic acid will be higher than the last group. Each new group will get a higher dose of carboplatin and/or valproic acid. If 1 of the 3 participants has a serious side effect at a certain dose level, 3 more participants may be added at that dose level to check the safety of the combination. If no more participants at that dose level have serious side effects, the next dose level will be tested. However, if a second participant has a serious side effect, then the dose level before that one will be considered the "maximum tolerated dose" (MTD). Once the MTD is found, participants will be enrolled on Phase 2 of the study.
Participants enrolled on Phase 2 were to be given the MTD level of the study drug combination; however, study did not progress to Phase 2.
Participants on both phases were to have the same treatment schedule and study tests performed. The only difference between Phase 1 and Phase 2 was to be the dose level of the study drug combination being given.
Study Treatment:
If eligible, participants received the study treatment on a 28-day treatment cycle.
On Day 1 of each cycle, they receive an injection of azacitidine just under the skin or by vein over 30 minutes once a day for 5 days in a row.
On Day 3 and Day 10 of each cycle, they receive carboplatin by vein over 60 minutes.
On Days 5-11 of each cycle, they take valproic acid by mouth once a day with or without food.
On Day 12 of each cycle, they may receive an injection of NeulastaTM (pegfilgrastim) just under the skin, depending on whether the study doctor thinks it is needed to help boost your white blood cell count.
On Days 13-28 of each cycle, they have a "rest period" from the study drugs before beginning a new 28-day cycle of treatment.
Study Visits:
At certain time points, they have the following tests/procedure performed during study visits:
On Day 5 and Day 11 of Cycles 1-3, about 1 tablespoon of blood drawn before treatment for molecular marker studies. These tests will be performed to look for a link between genetic characteristics and response to the study drug treatment.
Within the last 72 hours (3 days) of each cycle, blood drawn (about 1 tablespoon) and urine collected for routine tests. After the start of each cycle, blood drawn (about 1 tablespoon) once weekly for routine tests.
Within 7 days before starting each new cycle, evaluation to see if you may be experiencing any side effects.
After the end of every 2 cycles (about every 8 weeks), an x-ray and either a CT scan or an MRI scan to re-evaluate the cancer.
Length of Study:
Participants will continue to receive treatment on this study, as long as the disease does not get worse and you do not experience any intolerable side effects.
End-of-Treatment Visit:
Once treatment has ended for any reason, participants will come back for an end-of-treatment visit to have the following tests/procedures performed:
- You will have a complete physical exam.
- You will have urine collected and blood drawn (about 1 tablespoon) for routine tests.
- You may have a CT scan or an MRI scan to remeasure and re-evaluate the cancer.
Up to 65 patients were eligible to take part in this study. All were to be enrolled at M. D. Anderson. Study halted after Phase 1 without progressing to second phase.
- Conditions
- Solid Tumors
- Being tested
- Azacitidine, Valproic Acid, Carboplatin
- Keywords
- Advanced Cancer, Solid Tumors, Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer, Azacitidine, 5-Azacitidine, 5-Aza, Vidaza™, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Vidaza, Valproic Acid, Depakene, Carboplatin, Paraplatin
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
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
75 mg/m^2 Subcutaneous Injection or by vein Daily for 5 Days.
Valproic AcidDrug
Also called Depakene
40 mg/kg by mouth Daily for 7 days.
CarboplatinDrug
Also called Paraplatin
AUC 2 by vein on Days 3 and 10 over 60 Minutes.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine + Valproic Acid + Carboplatin | Experimental | Azacitidine 75 mg/m^2 subcutaneous injection or by vein daily for 5 Days. Valproic Acid 40 mg/kg by mouth daily for 7 days. Carboplatin area under the curve (AUC) 2 by vein on Days 3 and 10 over 60 Minutes. Receives: Drug: Azacitidine; Drug: Valproic Acid; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Assessment of tumor response by palpation, plain x-ray, MRI, or CT scan to be obtained after the first cycle and the every 2 cycles after that (8 weeks).
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2007 (estimated)
- Study startAug 2007
- Primary completionOct 2012
- Study completionOct 2012
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 Solid TumorsStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 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
- Gerald Falchook, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00529022
- Sponsor's protocol ID
- 2007-0030
- Status last verified
- Feb 2013
- First submitted
- 11 Sep 2007
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Falchook GS, Fu S, Naing A, Hong DS, Hu W, Moulder S, Wheler JJ, Sood AK, Bustinza-Linares E, Parkhurst KL, Kurzrock R. Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies. Invest New Drugs. 2013 Oct;31(5):1192-200. doi: 10.1007/s10637-013-0003-3. Epub 2013 Aug 2.
PubMed 23907406
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer
- ClinicalTrials.gov ID
- NCT00529022
- Acronym / sponsor ID
- 2007-0030
- Conditions
- Solid Tumors
- Keywords
- Advanced Cancer, Solid Tumors, Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer, Azacitidine, 5-Azacitidine, 5-Aza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Aug 2007
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 14 Sep 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.
The goal of this clinical research study is to find out if giving azacitidine with valproic acid plus carboplatin can help control advanced cancer. The safety of this treatment will be studied as well. Researchers will also collect some extra blood samples for molecular marker studies (studies that may help researchers predict how participants respond to the combined therapy).
There were to be two phases of this study: a Phase 1 portion to find acceptable doses of the study drug combination, and a Phase 2 portion to study the response rates to the treatment schedule. The study did not proceed to the Phase 2 portion.
Detailed description
The Study Drugs:
Researchers want to see if the combination of azacitidine, carboplatin, and valproic may work better together to control advanced cancer.
- Azacitidine is designed to activate ("turn on") certain genes in cancer cells whose job is to fight tumors, which may also make azacitidine work better with other anti-tumor drugs.
- Carboplatin is designed to block the growth of cancer cells by stopping cell division, which may cause the cells to die.
- Valproic acid is an anti-seizure medication that may also have cancer-fighting abilities. This drug may be able to activate tumor-fighting genes, causing cancer cells to die.
Phase 1 (Dose Escalation) and Phase 2 (Treatment):
Participants will be enrolled on Phase 1 of the study in groups of 3. Each group will receive a different combination of the study drugs. If the first group of 3 tolerates the study drug combination well, the next group of 3 will be enrolled, and their dose(s) of carboplatin and/or valproic acid will be higher than the last group. Each new group will get a higher dose of carboplatin and/or valproic acid. If 1 of the 3 participants has a serious side effect at a certain dose level, 3 more participants may be added at that dose level to check the safety of the combination. If no more participants at that dose level have serious side effects, the next dose level will be tested. However, if a second participant has a serious side effect, then the dose level before that one will be considered the "maximum tolerated dose" (MTD). Once the MTD is found, participants will be enrolled on Phase 2 of the study.
Participants enrolled on Phase 2 were to be given the MTD level of the study drug combination; however, study did not progress to Phase 2.
Participants on both phases were to have the same treatment schedule and study tests performed. The only difference between Phase 1 and Phase 2 was to be the dose level of the study drug combination being given.
Study Treatment:
If eligible, participants received the study treatment on a 28-day treatment cycle.
On Day 1 of each cycle, they receive an injection of azacitidine just under the skin or by vein over 30 minutes once a day for 5 days in a row.
On Day 3 and Day 10 of each cycle, they receive carboplatin by vein over 60 minutes.
On Days 5-11 of each cycle, they take valproic acid by mouth once a day with or without food.
On Day 12 of each cycle, they may receive an injection of NeulastaTM (pegfilgrastim) just under the skin, depending on whether the study doctor thinks it is needed to help boost your white blood cell count.
On Days 13-28 of each cycle, they have a "rest period" from the study drugs before beginning a new 28-day cycle of treatment.
Study Visits:
At certain time points, they have the following tests/procedure performed during study visits:
On Day 5 and Day 11 of Cycles 1-3, about 1 tablespoon of blood drawn before treatment for molecular marker studies. These tests will be performed to look for a link between genetic characteristics and response to the study drug treatment.
Within the last 72 hours (3 days) of each cycle, blood drawn (about 1 tablespoon) and urine collected for routine tests. After the start of each cycle, blood drawn (about 1 tablespoon) once weekly for routine tests.
Within 7 days before starting each new cycle, evaluation to see if you may be experiencing any side effects.
After the end of every 2 cycles (about every 8 weeks), an x-ray and either a CT scan or an MRI scan to re-evaluate the cancer.
Length of Study:
Participants will continue to receive treatment on this study, as long as the disease does not get worse and you do not experience any intolerable side effects.
End-of-Treatment Visit:
Once treatment has ended for any reason, participants will come back for an end-of-treatment visit to have the following tests/procedures performed:
- You will have a complete physical exam.
- You will have urine collected and blood drawn (about 1 tablespoon) for routine tests.
- You may have a CT scan or an MRI scan to remeasure and re-evaluate the cancer.
Up to 65 patients were eligible to take part in this study. All were to be enrolled at M. D. Anderson. Study halted after Phase 1 without progressing to second phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine + Valproic Acid + Carboplatin | Experimental | Drug: Azacitidine, Drug: Valproic Acid, Drug: CarboplatinAzacitidine 75 mg/m^2 subcutaneous injection or by vein daily for 5 Days. Valproic Acid 40 mg/kg by mouth daily for 7 days. Carboplatin area under the curve (AUC) 2 by vein on Days 3 and 10 over 60 Minutes. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patient has histologically or cytologically confirmed diagnosis of advanced solid tumor (that has progressed following standard therapy or for whom, in the opinion of the investigator, no standard effective therapy is available) during the phase I study. Only patients who have platinum resistant epithelial carcinoma of the ovary, fallopian tube or primary peritoneal carcinoma are enrolled onto the phase 2 study, if progresses to phase 2. According to standard Gynecologic Oncology Group (GOG) criteria platinum resistant is defined to have had a disease-free interval of shorter than 6 months following platinum treatment.
- Patient has measurable or evaluable disease by radiological imaging techniques with documented progression within 1 month before study entry or disease that has not responded to treatment. (Pleural effusions, ascites, osseous metastasis, elevation of tumor marker and lesions located in previously irradiated areas are not considered measurable).
- Patient is willing to comply with study procedures to have blood collections for correlative studies.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Patient must be informed of the investigational nature of this study and must sign and give written Internal Review Board (IRB) approved informed consent in accordance with institutional guidelines.
Key exclusion criteria (12 listed)
- Any concurrent chemotherapy.
- Underlying medical condition that might be aggravated by treatment or that cannot be controlled, such as active uncontrolled serious infection and cardiac dysfunction.
- Medical and psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
- Known hypersensitivity to azacitidine, valproic acid, carboplatin or their analogs.
- Failure to recover from any prior surgery within 4 weeks of study entry.
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-AZC75 mg/m^2 Subcutaneous Injection or by vein Daily for 5 Days. | Drug | Azacitidine + Valproic Acid + Carboplatin |
| Valproic AcidAlso: Depakene40 mg/kg by mouth Daily for 7 days. | Drug | Azacitidine + Valproic Acid + Carboplatin |
| CarboplatinAlso: ParaplatinAUC 2 by vein on Days 3 and 10 over 60 Minutes. | Drug | Azacitidine + Valproic Acid + Carboplatin |
Primary outcome
Response Rate
Time frame: 8 weeks
Assessment of tumor response by palpation, plain x-ray, MRI, or CT scan to be obtained after the first cycle and the every 2 cycles after that (8 weeks).
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 20 Feb 2013.
- Derived from this study: PubMed 23907406Falchook GS, Fu S, Naing A, Hong DS, Hu W, Moulder S, Wheler JJ, Sood AK, Bustinza-Linares E, Parkhurst KL, Kurzrock R. Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies. Invest New Drugs. 2013 Oct;31(5):1192-200. doi: 10.1007/s10637-013-0003-3. Epub 2013 Aug 2.
- The University of Texas M.D.Anderson Cancer CenterLink 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.
Gerald Falchook, 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, Valproic Acid and Carboplatin in people with Solid Tumors, 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 8 inclusion and 12 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 20 Feb 2013. 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?
Response Rate (time frame: 8 weeks). 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 NCT00529022, 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 20 Feb 2013.