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

NCT ID: NCT02159820

Last Updated: 2014-06-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2024-06-30

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.

Conditions

Primary Malignant Neoplasm of Ovary; FIGO Stages II to IV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DTC Arm

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

Group Type: ACTIVE_COMPARATOR

Decitabine (DTC Arm)

Intervention Type: 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.

TC regimen

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

Group Type: ACTIVE_COMPARATOR

Paclitaxel and Carboplatin (TC Arm)

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han weidong

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuanguang Meng, Professor

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Weidong Han, professor

Role: STUDY_CHAIR

Chinese PLA General Hospital

Locations

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yuanguang Meng, Professor

Role: CONTACT

mengyg@vip.sina.com

86-10-66938244

Yan Zhang, Dr.

Role: CONTACT

zhangyan@163.com

86-10-55499341

Facility Contacts

Yan Zhang, Dr.

Role: primary

zhangyan@163.com

86-10-55499341

References

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.

Reference Type: BACKGROUND

PMID: 24963497 (View on PubMed)

Related Links

http://www.cancer.gov

to recruit patients and let more oncologists know this trial

Other Identifiers

PLA-S-062

Identifier Type: -

Identifier Source: secondary_id

PLA-BT-010

Identifier Type: -

Identifier Source: org_study_id