Lower Dose Decitabine (DAC)-Primed TC (Carboplatin-Paclitaxel) Regimen in Ovary Cancer (DAC and CT)

Chinese PLA General Hospital (301 Hospital)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Primary Malignant Neoplasm of Ovary; FIGO Stages II to IV

Treatments: Drug: Paclitaxel and Carboplatin (TC Arm); Drug: Decitabine (DTC Arm)

Study type: Interventional

Funder types: Other

Identifiers

NCT02159820

PLA-S-062

PLA-BT-010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 estimated patients

Sex: Female

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 2 patient groups

DTC Arm

Active Comparator group

Description:

Patients are randomly assigned to receive lower-dose decitabine treatment followed by TC regimen (ie, DTC arm).

Treatment:

Drug: Decitabine (DTC Arm)

TC regimen

Active Comparator group

Description:

Patients were randomly assigned to receive carboplatin plus paclitaxel (ie, TC arm).

Treatment:

Drug: Paclitaxel and Carboplatin (TC Arm)