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

September 3, 2021 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

119

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy
        • Recruiting
        • Fondazione Irccs Istituto Nazionale Dei Tumori

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Decitabine plus Carboplatin
Carboplatin AUC 5 d 8 q 28 plus Decitabine 10 mg/mq iv d1-5 q 28
Drug: Carboplatin
Chemotherapy medication
Drug: Decitabine
Nucleic Acid Synthesis Inhibitor
Other: 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
Drug: Gemcitabine
Chemotherapy medication
Drug: Paclitaxel
Chemotherapy medication
Drug: Pegylated Liposomal Doxorubicin
Chemotherapy medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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)
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
from randomization to the date of death, assessed up to 3 years
Radiological response rate (in patients with measurable disease)
Time Frame: 3 years
Radiological response rate
3 years
Duration of response
Time Frame: 3 years
Duration of response
3 years
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.
3 years
Toxicity profile
Time Frame: 3 years
Incidence of adverse events
3 years
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.
3 years
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.
3 years
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.
3 years
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.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Domenica Lorusso, MD, National Cancer Institute (NCI)
  • Principal Investigator: Domenica Lorusso, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2018

Primary Completion (Anticipated)

December 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

February 16, 2018

First Submitted That Met QC Criteria

March 9, 2018

First Posted (Actual)

March 15, 2018

Study Record Updates

Last Update Posted (Actual)

September 5, 2021

Last Update Submitted That Met QC Criteria

September 3, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INT 189-17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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