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Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer. (MITO29)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03467178
Recruitment Status : Not yet recruiting
First Posted : March 15, 2018
Last Update Posted : March 16, 2018
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Tracking Information
First Submitted Date  ICMJE February 16, 2018
First Posted Date  ICMJE March 15, 2018
Last Update Posted Date March 16, 2018
Estimated Study Start Date  ICMJE April 2018
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
Progression free survival (PFS) [ Time Frame: from randomization to the date of radiological/clinical progression of disease or death, assessed up to 3 years ]
The primary objective is to compare Decitabine plus Carboplatin combination versus physician' choice chemotherapy in terms of progression free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • Overall survival (OS) [ Time Frame: from randomization to the date of death, assessed up to 3 years ]
    The secondary objective is to compare Decitabine plus Carboplatin combination versus physician' choice chemotherapy in terms of overall survival
  • Radiological response rate (in patients with measurable disease) [ Time Frame: 3 years ]
    Radiological response rate
  • Duration of response [ Time Frame: 3 years ]
    Duration of response
  • Cancer-Antigen 125 (CA-125) response rate per GCIG (Gynaecologic Cancer Intergroup) and change in CA-125 [ Time Frame: 3 years ]
    Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients.
  • Toxicity profile [ Time Frame: 3 years ]
    Incidence of adverse events
  • Patient Reported Outcome: Physical well-being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Social/family well-being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Functional well being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Emotional well being [ Time Frame: 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Overall survival (OS) [ Time Frame: from randomization to the date of death, assessed up to 3 years ]
    The secondary objective is to compare Decitabine plus Carboplatin combination versus physician' choice chemotherapy in terms of overall survival
  • Radiological response rate (in patients with measurable disease) [ Time Frame: 3 years ]
    Radiological response rate
  • Duration of response [ Time Frame: 3 years ]
    Duration of response
  • Cancer-Antigen 125 (CA-125) response rate per GCIG (Gynaecologic Cancer Intergroup) and change in CA-125 [ Time Frame: 3 years ]
    Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients.
  • Toxicity profile [ Time Frame: 3 years ]
    Incidence of adverse events
  • Patient Reported Outcome: Physical well-being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Social/family well-being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Functional well being [ Time Frame: 3 years ]
    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.
  • Patient Reported Outcome: Emotional well being [ Time Frame: 3 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer.
Official Title  ICMJE Randomized Phase II Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer.
Brief Summary

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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent, Platinum-resistant Ovarian Cancer
Intervention  ICMJE
  • Drug: Decitabine
    Nucleic Acid Synthesis Inhibitor
  • Drug: Carboplatin
    Chemotherapy medication
  • Drug: Pegylated Liposomal Doxorubicin
    Chemotherapy medication
  • Drug: Gemcitabine
    Chemotherapy medication
  • Drug: Paclitaxel
    Chemotherapy medication
Study Arms  ICMJE
  • Experimental: Decitabine plus Carboplatin
    Carboplatin AUC 5 d 8 q 28 plus Decitabine 10 mg/mq iv d1-5 q 28
    Interventions:
    • Drug: Decitabine
    • Drug: Carboplatin
  • Standard Treatment
    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
    Interventions:
    • Drug: Pegylated Liposomal Doxorubicin
    • Drug: Gemcitabine
    • Drug: Paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 9, 2018)
119
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. Hematopoietic: Leukocytes > 2,500/mm3; Absolute neutrophil count >1,500/mm3; Platelets count >100,000/mm3; Hemoglobin >9 g/dL
    2. 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

    3. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Domenica Lorusso, MD +390223903697 domenica.lorusso@istitutotumori.mi.it
Contact: Serena Giolitto, MSc +390223903882 serena.giolitto@istitutotumori.mi.it
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03467178
Other Study ID Numbers  ICMJE INT 189-17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study Sponsor  ICMJE Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Domenica Lorusso, MD National Cancer Institute (NCI)
PRS Account Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP