Primary Malignant Neoplasm of OvaryPhase 2/3DAC and CTNCT02159820
Lower Dose Decitabine (DAC)-Primed TC (Carboplatin-Paclitaxel) Regimen in Ovary Cancer
A Phase 2/3 study testing Decitabine (DTC Arm) and Paclitaxel and Carboplatin (TC Arm) in people with Primary Malignant Neoplasm of Ovary and FIGO Stages II to IV, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Most patients are typically diagnosed with advanced-stage disease. Platinum-paclitaxel regimen has been widely adopted as a standard first-line treatment for advanced ovarian cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Primary Malignant Neoplasm of Ovary, FIGO Stages II to IV
- What is being tested?
- Decitabine (DTC Arm) and Paclitaxel and Carboplatin (TC Arm)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteChina
- Study dates
- Jun 2014to Jun 2024
- Phase
- Phase 2/3
- 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 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages II to IV fallopian tube cancer, or primary peritoneal cancer. If only the results of cytological examinations were available, patients needed to have the following criteria: a cytological diagnosis of adenocarcinoma; an abdominal mass more than 2 cm in diameter on abdominal images; and a CA125 to carcinoembryonic antigen (CEA) ratio10 of more than 25, or no evidence of gastrointestinal cancer if CA125/CEA ratio was less than or equal to 25. Previous chemotherapy was not allowed.
- All patients had to be at least 18 years of age, to have an Eastern Cooperative
- Oncology Group (ECOG) performance status of 0-3, and were required to have adequate hematologic, renal, and hepatic function.
Who cannot join
- Patients were excluded if they had an ovarian tumour with a low malignant potential, or synchronous or metachronous (within 5 years) malignant disease other than carcinoma in situ.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Yan Zhang, Dr., 86-10-55499341, zhangyan@163.com
Yuanguang Meng, Professor
About this study
Official title: Addition of Decitabine to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Phase 2-3, Open-label, Randomised Controlled Trial
Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Most patients are typically diagnosed with advanced-stage disease. Platinum-paclitaxel regimen has been widely adopted as a standard first-line treatment for advanced ovarian cancer. Multiple collaborative randomised phase III trials evaluating the addition of a third chemotherapy agent, maintenance therapy or alternative taxanes failed to demonstrate significant improvements over a standard carboplatin/taxane doublet.
Decitabine (DAC), one major DNA demethylating agent, has been approved for treatment of preleukemic hematological disease myelodysplastic syndrome (MDS) by the Food and Drug Administration. Past trials of these with high doses, i.e., the use of maximal tolerated dose, for patients with solid tumors showed a low therapeutic index, due to extreme toxicities that have probably confounded the ability to document the true clinical response.
Read more
Low dose DNA demethylation agent decitabine (DAC) can resensitize the therapeutic indexes of resistent ovary cancer cells in vivo and in vitro.
The investigators hypothesized that DAC-triggered epigenetic reprogramming of tumor cells and possible immune cells could induce pronounced long-dated clinical effect by chemosensitization- and immunopotentiation-driven maximal eradicating roles on the minimal/residual lesions in primary patients with poor prognosis.
Read the detailed description
Given the poor prognosis and the currently existed therapeutic strategies, The investigators will perform a prospective, randomized, phase II to III, intergroup trial to compare carboplatin plus paclitaxel (TC) with the DAC-primed TC (DTC) regimen in previously untreated patients with stage II to IV ovarian cancer.
- Being tested
- Decitabine (DTC Arm), Paclitaxel and Carboplatin (TC Arm)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Decitabine (DTC Arm)Drug
Patients in DTC arm will receive lower-dose decitabine (7 mg/m2) administered intravenously within 1 hour for a consecutive 5 days, followed by TC regimen on day 6.
Paclitaxel and Carboplatin (TC Arm)Drug
The TC arm consisted of paclitaxel 150 mg/m2 administered intravenously (IV) over 3 hours followed by carboplatin (area under the curve [AUC] 5) administered by IV over 30 to 60 minutes both on day 1 of a 3-week schedule. Dose reductions were allowed depending on hematologic or nonhematologic toxicity, as follows: carboplatin AUC4; paclitaxel 135 mg/m2. Patients who achieved partial remission after six cycles could receive additional cycles on their physicians' discretion.
| Study group | Role | What they receive |
|---|---|---|
| DTC Arm | Active comparator | Patients are randomly assigned to receive lower-dose decitabine treatment followed by TC regimen (ie, DTC arm). Receives: Drug: Decitabine (DTC Arm) |
| TC regimen | Active comparator | Patients were randomly assigned to receive carboplatin plus paclitaxel (ie, TC arm). Receives: Drug: Paclitaxel and Carboplatin (TC Arm) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival in DTC treated advanced ovary cancer
The primary endpoint of this trial was progression-free survival (PFS), defined as the time from the date of randomisation to the date of the first occurrence of any of the following events: appearance of any new lesions that could be measured or assessed clinically; or CA125 criteria of disease progression. For patients with measurable disease, clinical or radiographical tumour measurements had priority over CA125 levels, and progression during treatment could not be declared on the basis of CA125 alone.
Measured: up to 20 months
Overall survival rate in DTC treated advanced ovary cancer
Overall survival (OS), defined as the time from random assignment to death as a result of any cause, response rate, and adverse events.response to treatment, toxicity, and quality of life. Toxicities were evaluated per course and per patient (worst score over all courses).
Measured: 30 months
Overall response rate in DTC treated advanced ovary cancer
Tumor measurements were made before each cycle by physical examination, before every third cycle by imaging methods in patients with measurable or evaluable disease, and after the last cycle. The same tumor assessment methods that were employed for baseline measurement were used for each repeat evaluation. Tumor response was graded according to Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 1 year
Toxicity in DTC treated advanced ovary cancer
Adverse events and toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NIC-CTC). Toxicities were recorded continuously; blood chemistry parameters were measured before each treatment cycle and weekly thereafter.Quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OV28 questionnaires.
Measured: 8 months
Secondary outcomes (1)
Pharmacokinetics of lower-dose decitabine
Blood samples were obtained prior to treatment and at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours after the first and fifth dose of decitabine. Plasma samples were stored and processed and further analyzed utilizing liquid chromatography/tandem mass spectrometry.
Peak plasma concentration (Cmax) or area under the plasma concentration versus time curve (AUC) will be obtained from more than 10 patients treated at a decitabine dose level of 7mg/m2/d.
Measured: up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
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 Primary Malignant Neoplasm of OvaryStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Yuanguang Meng, Professor, Principal investigator, Chinese PLA General HospitalWeidong Han, professor, Study chair, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02159820
- Sponsor's protocol ID
- PLA-BT-010
- Other IDs
- PLA-S-062
- Acronym
- DAC and CT
- Status last verified
- Jun 2014
- First submitted
- 1 Jun 2014
- Last updated
- 10 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fan H, Lu X, Wang X, Liu Y, Guo B, Zhang Y, Zhang W, Nie J, Feng K, Chen M, Zhang Y, Wang Y, Shi F, Fu X, Zhu H, Han W. Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report. J Immunol Res. 2014;2014:371087. doi: 10.1155/2014/371087. Epub 2014 May 21.
PubMed 24963497
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Decitabine to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Phase 2-3, Open-label, Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02159820
- Acronym / sponsor ID
- DAC and CT / PLA-BT-010
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 10 Jun 2014 (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.
Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Most patients are typically diagnosed with advanced-stage disease. Platinum-paclitaxel regimen has been widely adopted as a standard first-line treatment for advanced ovarian cancer. Multiple collaborative randomised phase III trials evaluating the addition of a third chemotherapy agent, maintenance therapy or alternative taxanes failed to demonstrate significant improvements over a standard carboplatin/taxane doublet.
Decitabine (DAC), one major DNA demethylating agent, has been approved for treatment of preleukemic hematological disease myelodysplastic syndrome (MDS) by the Food and Drug Administration. Past trials of these with high doses, i.e., the use of maximal tolerated dose, for patients with solid tumors showed a low therapeutic index, due to extreme toxicities that have probably confounded the ability to document the true clinical response.
Low dose DNA demethylation agent decitabine (DAC) can resensitize the therapeutic indexes of resistent ovary cancer cells in vivo and in vitro.
The investigators hypothesized that DAC-triggered epigenetic reprogramming of tumor cells and possible immune cells could induce pronounced long-dated clinical effect by chemosensitization- and immunopotentiation-driven maximal eradicating roles on the minimal/residual lesions in primary patients with poor prognosis.
Detailed description
Given the poor prognosis and the currently existed therapeutic strategies, The investigators will perform a prospective, randomized, phase II to III, intergroup trial to compare carboplatin plus paclitaxel (TC) with the DAC-primed TC (DTC) regimen in previously untreated patients with stage II to IV ovarian cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DTC Arm | Active comparator | Drug: Decitabine (DTC Arm)Patients are randomly assigned to receive lower-dose decitabine treatment followed by TC regimen (ie, DTC arm). |
| TC regimen | Active comparator | Drug: Paclitaxel and Carboplatin (TC Arm)Patients were randomly assigned to receive carboplatin plus paclitaxel (ie, TC arm). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages II to IV fallopian tube cancer, or primary peritoneal cancer. If only the results of cytological examinations were available, patients needed to have the following criteria: a cytological diagnosis of adenocarcinoma; an abdominal mass more than 2 cm in diameter on abdominal images; and a CA125 to carcinoembryonic antigen (CEA) ratio10 of more than 25, or no evidence of gastrointestinal cancer if CA125/CEA ratio was less than or equal to 25. Previous chemotherapy was not allowed.
- All patients had to be at least 18 years of age, to have an Eastern Cooperative
- Oncology Group (ECOG) performance status of 0-3, and were required to have adequate hematologic, renal, and hepatic function.
Key exclusion criteria (1 listed)
- Patients were excluded if they had an ovarian tumour with a low malignant potential, or synchronous or metachronous (within 5 years) malignant disease other than carcinoma in situ.
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 |
|---|---|---|
| Decitabine (DTC Arm)Patients in DTC arm will receive lower-dose decitabine (7 mg/m2) administered intravenously within 1 hour for a consecutive 5 days, followed by TC regimen on day 6. | Drug | DTC Arm |
| Paclitaxel and Carboplatin (TC Arm)The TC arm consisted of paclitaxel 150 mg/m2 administered intravenously (IV) over 3 hours followed by carboplatin (area under the curve [AUC] 5) administered by IV over 30 to 60 minutes both on day 1 of a 3-week schedule. Dose reductions were allowed depending on hematologic or nonhematologic toxicity, as follows: carboplatin AUC4; paclitaxel 135 mg/m2. Patients who achieved partial remission after six cycles could receive additional cycles on their physicians' discretion. | Drug | TC regimen |
Primary outcome
Progression-free survival in DTC treated advanced ovary cancer
Time frame: up to 20 months
The primary endpoint of this trial was progression-free survival (PFS), defined as the time from the date of randomisation to the date of the first occurrence of any of the following events: appearance of any new lesions that could be measured or assessed clinically; or CA125 criteria of disease progression. For patients with measurable disease, clinical or radiographical tumour measurements had priority over CA125 levels, and progression during treatment could not be declared on the basis of CA125 alone.
Overall survival rate in DTC treated advanced ovary cancer
Time frame: 30 months
Overall survival (OS), defined as the time from random assignment to death as a result of any cause, response rate, and adverse events.response to treatment, toxicity, and quality of life. Toxicities were evaluated per course and per patient (worst score over all courses).
Overall response rate in DTC treated advanced ovary cancer
Time frame: 1 year
Tumor measurements were made before each cycle by physical examination, before every third cycle by imaging methods in patients with measurable or evaluable disease, and after the last cycle. The same tumor assessment methods that were employed for baseline measurement were used for each repeat evaluation. Tumor response was graded according to Response Evaluation Criteria in Solid Tumors (RECIST).
Toxicity in DTC treated advanced ovary cancer
Time frame: 8 months
Adverse events and toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NIC-CTC). Toxicities were recorded continuously; blood chemistry parameters were measured before each treatment cycle and weekly thereafter.Quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OV28 questionnaires.
1 secondary outcome
Pharmacokinetics of lower-dose decitabine
Time frame: up to 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2014.
- Background: PubMed 24963497Fan H, Lu X, Wang X, Liu Y, Guo B, Zhang Y, Zhang W, Nie J, Feng K, Chen M, Zhang Y, Wang Y, Shi F, Fu X, Zhu H, Han W. Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report. J Immunol Res. 2014;2014:371087. doi: 10.1155/2014/371087. Epub 2014 May 21.
- to recruit patients and let more oncologists know this trialLink 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.
Yuanguang Meng, Professor principal investigator
Chinese PLA General Hospital
Weidong Han, professor study chair
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Decitabine (DTC Arm) and Paclitaxel and Carboplatin (TC Arm) in people with Primary Malignant Neoplasm of Ovary and FIGO Stages II to IV, run by Chinese PLA General Hospital at 1 site in China.
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 3 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 10 Jun 2014. 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 China. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yuanguang Meng, Professor (86-10-66938244, mengyg@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival in DTC treated advanced ovary cancer (time frame: up to 20 months). The study lists 4 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 NCT02159820, 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 10 Jun 2014.