Lower Dose Decitabine (DAC)-Primed TC (Carboplatin-Paclitaxel) Regimen in Ovary Cancer (DAC and CT)
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|ClinicalTrials.gov Identifier: NCT02159820|
Recruitment Status : Recruiting
First Posted : June 10, 2014
Last Update Posted : June 10, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Primary Malignant Neoplasm of Ovary FIGO Stages II to IV||Drug: Decitabine (DTC Arm) Drug: Paclitaxel and Carboplatin (TC Arm)||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||June 2024|
|Estimated Study Completion Date :||June 2024|
Active Comparator: DTC Arm
Patients are randomly assigned to receive lower-dose decitabine treatment followed by TC regimen (ie, DTC arm).
Drug: 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.
Active Comparator: TC regimen
Patients were randomly assigned to receive carboplatin plus paclitaxel (ie, TC arm).
Drug: 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.
- 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.
- Pharmacokinetics of lower-dose decitabine [ Time Frame: up to 8 weeks ]
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.
- Pharmacodynamics of lower-dose decitabine [ Time Frame: up to 8 weeks ]To assess the pharmacodynamics of decitabine and to establish its relationship to clinical PFS, before and after decitabine treatment, peripheral blood mononuclear cells and/or tumor samples will be harvested for measurement of the expression and methylation profile including genes such as MLH1, RASSF1A, HOXA10, and HOXA11 by quantitative polymerase chain reaction (qPCR) and methylation-sensitive PCR analyses.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159820
|Contact: Yuanguang Meng, Professoremail@example.com|
|Contact: Yan Zhang, Dr.||firstname.lastname@example.org|
|Chinese PLA General Hospital||Recruiting|
|Beijing, Beijing, China, 100853|
|Contact: Yan Zhang, Dr. 86-10-55499341 email@example.com|
|Principal Investigator: Yuanguang Meng, Professor|
|Principal Investigator:||Yuanguang Meng, Professor||Chinese PLA General Hospital|
|Study Chair:||Weidong Han, professor||Chinese PLA General Hospital|