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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 _MITO-23 (Mito23)

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ClinicalTrials.gov Identifier: NCT02903004
Recruitment Status : Recruiting
First Posted : September 16, 2016
Last Update Posted : September 16, 2016
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Drug: Trabectedin Drug: Pegylated Liposomal Doxorubicin Drug: Topotecan Drug: Gemcitabine Drug: Weekly Paclitaxel Drug: Carboplatin Phase 3

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  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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_MITO-23
Study Start Date : April 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Trabectedin

Arm Intervention/treatment
Experimental: Trabectedin
Trabectedin 1.3 mg/m2 d1 q 21 in 3 hours (central line)
Drug: Trabectedin
Other Name: Yondelis

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: Pegylated Liposomal Doxorubicin
Drug: Topotecan
Drug: Gemcitabine
Drug: Weekly Paclitaxel
Drug: Carboplatin



Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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].

  2. Duration of Response [ Time Frame: 4 years ]
    Duration of response

  3. Adverse events [ Time Frame: 4 years ]
    Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903004


Contacts
Contact: Domenica Lorusso, MD +390223903697 domenica.lorusso@istitutotumori.mi.it
Contact: Elisa Grassi +390223903818 trialcenter@istitutotumori.mi.it

Locations
Italy
Domenica Lorusso Recruiting
Milan, Italy, 20133
Contact: Domenica Lorusso, MD    +390223903697    domenica.lorusso@istitutotumori.mi.it   
Contact: Elisa Grassi    +390223903818    elisa.grassi@istitutotumori.mi.it   
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: Domenica Lorusso, MD Fondazione IRCCS Istituto Nazionale Tumori

Publications of Results:

Other Publications:
Salutari V, Ferrandina G, Vincenzi B et al. Efficacy and safety outcomes in heavily pretreated patients (pts) with relapsed ovarian cancer (roc ) after single agent trabectedin. ASCO 2013, submitted.
Monk BJ, Herzog T, Kay S et al. A randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in relapsed, recurrent ovarian cancer (OC). Ann. Oncol. 19(Suppl. 8), (2009)
K. L. Tedesco, J. L. Blum, A. Goncalves, J. Lubinski, N. Ben-Baruch, C. R. Osborne, P. Lardelli, A et al. phase II trial of trabectedin (T) in patients (pts) with HER2-positive and BRCA1/2 germ-line-mutated metastatic breast cancer (MBC). J Clin Oncol 28:15s, 2010 (suppl; abstr 1038)

Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT02903004     History of Changes
Other Study ID Numbers: INT 181/15
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: September 16, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Gemcitabine
Liposomal doxorubicin
Trabectedin
Carboplatin
Doxorubicin
Topotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents