Trial on Trabectedin (ET-743) vs Clinician's Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients (MITO23)

August 24, 2021 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Randomized Phase III Trial on Trabectedin (ET-743) vs Clinician's Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients

This is an open-label, prospective, multicenter, randomized Phase III, clinical trial evaluating the efficacy and safety of trabectedin in BRCA1 and BRCA2 mutation carrier and BRCAness phenotype advanced ovarian cancer patients in comparison to physician' choice chemotherapy.

Arm A: Trabectedin 1.3 mg/mq d1 q 21 in 3 hours (central line) Arm B: Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Topotecan 4 mg/mq dd 1,8,15 q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 Weekly Paclitaxel 80 mg/mq gg 1, 8, 15 q 28 Carboplatin AUC 5-6 q 21 or 28

Patients will be randomly assigned in a 1:1 ratio to treatment arms. During the randomization process, patients will be stratified by

  • Platinum sensitivity
  • Measurable disease
  • Number of previous chemotherapy lines > vs < 3
  • BRCA mutational status

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Subjects will be randomized in a 1:1 ratio to receive one of the following treatments: Arm A: Trabectedin 1.3 mg/m2 d1 q 21 in 3 hours (central line) Arm B: Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Topotecan 4 mg/ m2 dd 1,8,15 q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 Weekly Paclitaxel 80 mg/ m2 dd 1, 8, 15 q 28 Carboplatin AUC 5-6 q 21 or 28 Randomization will be stratified based on platinum-free interval (PFI) (PFI ≥ 0 and ≤ 6 months vs. PFI > 6 months), presence / absence of measurable disease/number of previous chemotherapy lines, germline BRCA mutational status vs BRCAness phenotype.

Platinum-free interval (PFI) is defined as the time from the last dose of the platinum containing regimen until the first date progression.

Subjects will continue to receive chemotherapy treatment until disease progression (clinical progression meant as global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression is considered progression of disease), intolerability, patient refusal, investigator decision or death from any cause.

Subjects will be evaluated every 12 weeks ± 1 week by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for objective radiographic response and radiographic disease progression.

Study Type

Interventional

Enrollment (Actual)

242

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Italy
      • Rome, Italy, 00168
        • Domenica Lorusso

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:

  1. Female of age 18 years or older
  2. Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

  3. Platinum resistant or sensitive patients with either:

    1. BRCA mutated patients
    2. BRCAness phenotype patients: patients who have received and responded (subsequent PFI>6 months) to at least 2 previous platinum based chemotherapy lines
    3. Platinum sensitive patients who are not able to receive or not willing to receive other platinum treatments
  4. Measurable and evaluable disease per RECIST 1.1(Subjects with isolated rising CA-125 without radiologically visible disease are excluded)
  5. ECOG performance status 0 or 1
  6. No limits in the number of previous chemotherapy lines, previous treatment with parp inhibitors is allowed
  7. Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal
  8. Life expectancy of at least 3 months

  9. Adequate organ functions:

    1. Hematopoietic: Absolute neutrophil count ≥ 1,500/mm3; Platelet count ≥ 100,000/mm3; Hemoglobin ≥ 9 g/dl
    2. Hepatic: AST and ALT ≤ 1.5 times upper limit of normal (ULN)* ; Alkaline Phosphatase ≤ 2.5 times ULN* ; Bilirubin ≤ 1.5 times ULN. NOTE: * ≤ 3 times ULN if liver metastases are present
    3. Renal: Creatinine Clearance ≥ 45 ml/min or Serum Creatinine ≤1.5 x ULN
    4. Serum Albumin >2.5 g/dl
  10. No other invasive malignancy within the past 3 years except non-melanoma skin cancer or in situ cervical cancer (patients with previous cancers may be enrolled providing that no recurrences have be reported in the last 3 years)
  11. Written Informed Consent
  12. Adequately recovered from the acute toxicity of any prior treatment
  13. For agents in the standard arm, also refer to the local prescribing information with regards to warnings, precautions, and contraindications

Exclusion Criteria:

  1. Prior exposure to trabectedin
  2. Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
  3. Subjects with borderline ovarian cancer, ie. Subject with low malignant potential tumors are excluded
  4. Less than 2 reported responses to platinum (i.e. subsequent recurrences at least 6 months after the first and the second platinum based treatment), unless BRCA mutation is documented.
  5. Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy
  6. History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer
  7. Known clinically relevant CNS metastases, unless treated and asymptomatic

  8. Other serious illnesses, such as:

    1. Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrolment; uncontrolled arterial hypertension or arrhythmias.
    2. Psychiatric disorder that prevents compliance with protocol.
    3. Active viral hepatitis; or chronic liver disease.
    4. Active infection.
    5. Any other unstable medical conditions.

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: Trabectedin
Trabectedin 1.3 mg/m2 d1 q 21 in 3 hours (central line)
Drug: Trabectedin
Other Names:
  • Yondelis
Other: Standard Treatment
Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Topotecan 4 mg/ m2 dd 1,8,15 q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 Weekly Paclitaxel 80 mg/ m2 dd 1, 8, 15 q 28 Carboplatin AUC 5-6 q 21 or 28
Drug: Gemcitabine
Drug: Carboplatin
Drug: Topotecan
Drug: Pegylated Liposomal Doxorubicin
Drug: Weekly Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 4 years
The primary objective is to compare the Trabectedin versus physician' choice chemotherapy in terms of overall survival (OS).
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: 4 years
Progression-free survival [the diagnosis of progression will be assessed by radiological criteria; CA 125 increases alone (GCIG criteria of progression) will not be considered as progression of disease without a radiological confirmation of progression].
4 years
Duration of Response
Time Frame: 4 years
Duration of response
4 years
Adverse events
Time Frame: 4 years
Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.
4 years

Collaborators and Investigators

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

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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)

April 11, 2016

Primary Completion (Actual)

December 20, 2018

Study Completion (Actual)

December 20, 2018

Study Registration Dates

First Submitted

August 26, 2016

First Submitted That Met QC Criteria

September 12, 2016

First Posted (Estimate)

September 16, 2016

Study Record Updates

Last Update Posted (Actual)

August 25, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 986

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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