Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer.

Study Overview
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Brief Summary
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Multicenter Phase II study on Decitabine-Carboplatin combination in platinum resistant ovarian cancer patients. Patients will receive study treatment until disease progression is documented, extraordinary medical circumstances occur, intolerable toxicities occur, or the patient withdraws consent.

Detailed Description
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This is an open-label, prospective, multicenter, randomized Phase II, clinical trial evaluating the efficacy and safety of Decitabine-Carboplatin combination in recurrent, platinum resistant ovarian cancer patients in comparison to physician' choice chemotherapy: Arm A: Carboplatin AUC (Area Under Curve) 5 d 8 q 28 Plus Decitabine 10 mg/mq iv d1-5 q 28 Arm B: Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 or Weekly Paclitaxel 80 mg/mq gg 1, 8, 15 q 28 Patients will be randomly assigned in a 1:1 ratio to treatment arms.

Official Title
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Randomized Phase II Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer.

Conditions
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Recurrent, Platinum-resistant Ovarian Cancer

Intervention / Treatment
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* Drug: Decitabine
* Drug: Carboplatin
* Drug: Pegylated Liposomal Doxorubicin
* Drug: Gemcitabine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologic / histologic diagnosis of stage 1°C-4° epithelial , fallopian tube and primary peritoneal cancer (carcinosarcomas are included) Patient who received 1-2 prior lines of treatments Patient relapsed within 6 months after platinum containing regimen Disease measurable or evaluable by RECIST version 1.1 or Ca 125 GCIG criteria (Gynaecologic Cancer Intergroup). No residual peripheral neurotoxicity > Grade 1 from previous chemotherapy treatment Performance Status (PS) 0-1 Age 18 years. Life expectancy of at least 3 months Written informed consent prior to performance of study specific procedures or assessments Ability and willingness to comply with treatment and follow up assessments and procedures Adequate organ functions: Hematopoietic: Leukocytes > 2,500/mm3; Absolute neutrophil count >1,500/mm3; Platelets count >100,000/mm3; Hemoglobin >9 g/dL Hepatic: AST (aspartate transaminase ) and ALT (alanine transaminase) <3 times upper limit of normal (ULN)*; Alkaline phosphatase <3 times ULN*; Bilirubin <1.5 times ULN *: <5 times ULN if liver metastases are present Renal: Creatinine clearance >45 mL/min No other invasive malignancy within the past 3 years except non-melanoma skin cancer and in situ cervical cancer Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule. Exclusion Criteria: Pregnant (potentially fertile patients must use contraceptive measures to avoid pregnancy during and for at least 3 months after study participation and must have a negative serum pregnancy test at baseline). Patients should not be breast-feeding during treatment and for 2 months following the end of treatment. Serious heart disease, including heart failure, atrio-ventricular block of any degree, serious arrhythmia or history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA) Active infection requiring antibiotics. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. Patients who had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with < Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. Patients with evidence of interstitial lung disease. Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedures such as fine needle aspiration or core biopsy within 1 week prior to beginning therapy are also excluded. Known hypersensitivity to the study drugs or to drugs with similar chemical structures. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine plus Carboplatin<br>Carboplatin AUC 5 d 8 q 28 plus Decitabine 10 mg/mq iv d1-5 q 28 | Drug: Decitabine<br>* Nucleic Acid Synthesis Inhibitor<br>Drug: Carboplatin<br>* Chemotherapy medication<br>|
| Other: Standard Treatment<br>Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 or Weekly Paclitaxel 80 mg/ m2 dd 1, 8, 15 q 28 | Drug: Pegylated Liposomal Doxorubicin<br>* Chemotherapy medication<br>Drug: Gemcitabine<br>* Chemotherapy medication<br>Drug: Paclitaxel<br>* Chemotherapy medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The primary objective is to compare Decitabine plus Carboplatin combination versus physician' choice chemotherapy in terms of progression free survival | from randomization to the date of radiological/clinical progression of disease or death, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The secondary objective is to compare Decitabine plus Carboplatin combination versus physician' choice chemotherapy in terms of overall survival | from randomization to the date of death, assessed up to 3 years | 
| Radiological response rate (in patients with measurable disease) | Radiological response rate | 3 years | 
| Duration of response | Duration of response | 3 years | 
| Cancer-Antigen 125 (CA-125) response rate per GCIG (Gynaecologic Cancer Intergroup) and change in CA-125 | Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. | 3 years | 
| Toxicity profile | Incidence of adverse events | 3 years | 
| Patient Reported Outcome: Physical well-being | will be evaluated using the Functional Assessment of Cancer Therapy (FACT-O) and FACT-O Ovarian Cancer-specific Subscale (OCS) questionnaire. The total scores of both scales will be calculated, the scores of each question at each time point and their difference from baseline will be summarized for each treatment group. At a given visit, the change and/or percent change from baseline will be compared between the randomized treatment groups using an ANCOVA test using the treatment as a categorical factor and baseline measurement for the parameter as a continuous covariate. The time to an event in PRO (Patient Reported Outcome) of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire. Patients without a 4-point reduction will be censored on the date of their last PRO evaluation. Patients that do not have both a baseline measurement and at least one post-baseline measurement will not be included. | 3 years | 
| Patient Reported Outcome: Social/family well-being | will be evaluated using the Functional Assessment of Cancer Therapy (FACT-O) and FACT-O ovarian cancer-specific subscale (OCS) questionnaire. The total scores of both scales will be calculated, the scores of each question at each time point and their difference from baseline will be summarized for each treatment group. At a given visit, the change and/or percent change from baseline will be compared between the randomized treatment groups using an ANCOVA test using the treatment as a categorical factor and baseline measurement for the parameter as a continuous covariate. The time to an event in PRO of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire. Patients without a 4-point reduction will be censored on the date of their last PRO evaluation. Patients that do not have both a baseline measurement and at least one post-baseline measurement will not be included. | 3 years | 
| Patient Reported Outcome: Functional well being | will be evaluated using the Functional Assessment of Cancer Therapy (FACT-O) and FACT-O ovarian cancer-specific subscale (OCS) questionnaire. The total scores of both scales will be calculated, the scores of each question at each time point and their difference from baseline will be summarized for each treatment group. At a given visit, the change and/or percent change from baseline will be compared between the randomized treatment groups using an ANCOVA test using the treatment as a categorical factor and baseline measurement for the parameter as a continuous covariate. The time to an event in PRO of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire. Patients without a 4-point reduction will be censored on the date of their last PRO evaluation. Patients that do not have both a baseline measurement and at least one post-baseline measurement will not be included. | 3 years | 
| Patient Reported Outcome: Emotional well being | will be evaluated using the Functional Assessment of Cancer Therapy (FACT-O) and FACT-O ovarian cancer-specific subscale (OCS) questionnaire. The total scores of both scales will be calculated, the scores of each question at each time point and their difference from baseline will be summarized for each treatment group. At a given visit, the change and/or percent change from baseline will be compared between the randomized treatment groups using an ANCOVA test using the treatment as a categorical factor and baseline measurement for the parameter as a continuous covariate. The time to an event in PRO of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire. Patients without a 4-point reduction will be censored on the date of their last PRO evaluation. Patients that do not have both a baseline measurement and at least one post-baseline measurement will not be included. | 3 years |