FIGO Stages II to IV Clinical Trial
— DAC and CTOfficial 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.
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.
| Status | Recruiting |
| Enrollment | 500 |
| Est. completion date | June 2024 |
| Est. primary completion date | June 2024 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years to 80 Years |
| Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| China | Chinese PLA General Hospital | Beijing | Beijing |
| Lead Sponsor | Collaborator |
|---|---|
| Chinese PLA General Hospital |
China,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Pharmacodynamics of lower-dose decitabine | 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. | up to 8 weeks | Yes |
| Primary | 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. | up to 20 months | Yes |
| Primary | 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). | 30 months | Yes |
| Primary | 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). | 1 year | Yes |
| Primary | 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. | 8 months | Yes |
| Secondary | 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. |
up to 8 weeks | Yes |