Ovarian Cancer
Conditions
Brief summary
Ovarian cancer (OC) is the leading cause of death from gynecologic cancer. It is estimated that 22,440 new cases of EOC will be diagnosed in 2017 with an estimated 14,080 EOC deaths. Several different histological subtypes of OC can be identified. Over 90% of malignant ovarian tumors are epithelial cancers (EOC), which are then classified into 5 broad histological subtypes: serous, endometrioid, mucinous, clear cell and mixed or carcinosarcomatous mullerian tumors. Almost 10 years ago, a new classification was proposed that separated ovarian cancers into type I and II tumors. Type II tumors included high-grade serous, which frequently contain mutations in p53, NF1, BRCA1, and BRCA2 and CDK125. Serous carcinomas represent the vast majority of primary malignant ovarian tumors (75%-80%), among these high-grade serous (HGSOC) accounts for 85%-90% and for the majority of the deaths due to ovarian cancer. The 5-year survival rate for EOC is only 46% because \>60% of patients are diagnosed with advanced disease. Patients with advanced stage EOC are typically managed with cytoreductive surgery and perioperative platinum-based chemotherapy, either in the adjuvant setting or with neoadjuvant chemotherapy and interval debulking surgery. Although primary advanced stage EOC is initially sensitive to this treatment paradigm, \>75% will eventually recur. Patients with recurrent disease are treated with additional lines of chemotherapy that may increase survival but is ultimately not curative. Given the high relapse rate and poor prognosis of advanced stage EOC, interest is increasing in the development of new approaches to treat recurrent EOC.
Interventions
None listed
Sponsors
Centro di Riferimento Oncologico - Aviano
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of a first relapse of high-grade ovarian cancer (≥12 months after the last platinum administration); * p53 positive tumors evaluated by IHC (\>30% of stained tumor cells); * Performance Status (Eastern Cooperative Oncology Group scale, ECOG) ≤ 2;- Availability of the tumor sample for immunohistochemical analysis; * Written informed consent.
Exclusion criteria
* Pre-existing or concurrent tumors, except in situ carcinoma or basophilic carcinoma of the skin; * Low p53 expression levels (\<30% of stained tumor cells); * Persistent grade≥ 2 neuropathy; * Severe heart disease; * Surgeon's decision of a second curative surgery; * Uncontrolled active infections; * Insufficient patient compliance; * Absence of signed informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess DNA-PK as a potential predictive biomarker for distinguishing patients who will benefit from CBDCA/TAX therapy from those who will respond more favorably to the CBDCA/PLD regimen, based on DNA-PK expression levels. | up to 5 years | Two years progression free survival will be estimated with Kaplan-Meier methods and reported as survival probability in the two treatment groups. PFS will be defined as time from the beginning of second line platinum based therapy and progression or death or end of follow-up whichever comes first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Response Rate | up to 5 years | Response rate will be reported as numbers and percentages and evaluated based on RECIST 1.1 criteria |
| Evaluation of Overall Survival in the different treatment regimens | Up to 5 years | Overall Survival (OS) will be evaluated with Kaplan-Meier methods and reported separately for the two treatment groups. OS will be defined as time from the beginning of second line platinum based therapy and death or end of follow-up whichever comes first |
| PFS in patients treated with biomarker driven therapy and physician's choice therapy | up to 5 years | Difference in PFS between subgroups of patients will be evaluated with Kaplan-Meier method and log-rank test |
| OS in patients treated with biomarker driven therapy and physician's choice therapy | up to 5 years | Difference in OS between subgroups of patients will be evaluated with Kaplan-Meier method and log-rank test |
Countries
Italy
Outcome results
None listed