Clinical trial NCT02159820: Lower Dose Decitabine (DAC)-Primed TC (Carboplatin-Paclitaxel) Regimen in Ovary Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Primary Malignant Neoplasm of Ovary
FIGO Stages II to IV
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2014-06-10
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free survival in DTC treated advanced ovary cancer
timeFrame: up to 20 months
measure: Overall survival rate in DTC treated advanced ovary cancer
timeFrame: 30 months
measure: Overall response rate in DTC treated advanced ovary cancer
timeFrame: 1 year
measure: Toxicity in DTC treated advanced ovary cancer
timeFrame: 8 months
Secondary outcomes:
measure: Pharmacokinetics of lower-dose decitabine
timeFrame: up to 8 weeks
Other outcomes:
measure: Pharmacodynamics of lower-dose decitabine
timeFrame: up to 8 weeks
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Yuanguang Meng, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Weidong Han, professor
role: STUDY_CHAIR
References:
citation: 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.