A Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2012-004808-34-GB
• Date of registration: 24/04/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
• Scientific title: A Randomized, Open-Label Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX Monotherapy for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
• Date of first enrolment: 11/07/2013
• Target sample size: 582
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004808-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, China, Israel, New Zealand, Poland, Russian Federation, South Africa, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically proven advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Received first-line treatment with a platinum-based regimen and had no evidence of disease progression for 6 months after the last dose
- Received second-line treatment with a platinum-based regimen, with progression of disease after attaining a complete response (CR) or partial response (PR)
-progression of disease based on imaging after the second-line platinum-based regimen (individuals treated with a DOXIL-containing regimen as a second-line therapy are eligible if subsequent disease progression occurs >=9 months from the first dose)
- Evidence of measurable disease at screening as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)
-Criterion modified per amendment: per Amendment 6, subjects no
longer need to be able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid
- Have a known BRCA 1/2 mutation status (for participants who do not have a known BRCA 1/2 status at screening, a blood sample will be collected to determine the status with the results available prior to randomization
- Laboratory values within protocol -defined parameters
- Have left ventricular ejection fraction by multigated acquisition scan (MUGA) scan or 2D-ECHO within normal limits for the institution
- Have side effects (except alopecia) of prior treatment resolved to at least Grade 1 according to the National Cancer Institute – Common Terminology Criteria of Adverse Events (NCI-CTCAE) (Version 4.0)
- Have a negative urine or serum pregnancy test at screening
- Agrees to protocol-defined use of effective contraception

Please refer to protocol for full inclusion criteria

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 582
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 582

Exclusion criteria:
- Diagnosis of ovarian carcinoma with mucinous histology
- Had more than 2 prior lines of chemotherapy
- Criterion modified per amendment: per Amendment 6, subjects who had a Prior exposure to trabectedin or hypersensitivity to any of the excipients will not be excluded from receiving single-agent DOXIL
- Prior treatment with doxorubicin or other anthracycline at cumulative doses greater than 300 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1 mg Doxil= 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
- Criterion modified per amendment: per Amendment 6, subjects unwilling or unable to have a central venous catheter placed will not be excluded from receiving single-agent DOXIL
- Pregnant or breast-feeding
- Less than 3 weeks from radiation therapy, experimental therapy, hormonal therapy, prior chemotherapy, or biological therapy
- History of another neoplastic disease (except non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ adequately treated) unless in remission for 5 years
- Known allergies, hypersensitivity, or intolerance to Doxil, dexamethasone, or their excipients
- Known history of central nervous system metastasis
- Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential participants who test positive for hepatitis B surface antigen or hepatitis C antibodies are allowed provided they do not have active disease requiring antiviral therapy)
- Had a myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- Has any of the following medical conditions: uncontrolled diabetes, psychiatric disorder (including dementia) that prevents compliance with protocol, uncontrolled seizures, newly diagnosed deep vein thrombosis, active systemic infection that is likely to interfere with study procedure or results
- Has any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements

Please refer to protocol for full exclusion criteria


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Ovarian cancer
MedDRA version: 20.0 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864

Intervention(s)

Trade Name: YONDELIS
Product Name: Trabectedin
Product Code: GFI-17027907-AAA-PB-003
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRABECTEDIN
CAS Number: 114899-77-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: CAELYX
Product Name: Caelyx
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Caelyx
Other descriptive name: DOXORUBICIN HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Primary end point(s): • Overall survival

Secondary Objective: - To evaluate PFS.
- To evaluate the objective response rate (ORR).
- To characterize the plasma pharmacokinetics of trabectedin using a sparse sampling scheme in the
trabectedin+DOXIL treatment group.
- To evaluate the safety of the trabectedin+DOXIL combination therapy and DOXIL monotherapy

Main Objective: To compare the OS after treatment with trabectedin+DOXIL combination therapy to that observed after treatment with DOXIL monotherapy for subjects with platinum-sensitive advanced-relapsed epithelial
ovarian, primary peritoneal, or fallopian tube cancer who have received 2 previous lines of platinum-based chemotherapy.

Timepoint(s) of evaluation of this end point: up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been observed, whichever is later
Following Amendment 6, study data collection including laboratory tests,
cardiovascular monitoring, physical examinations, tumour assessments,
PROs, and ECOG status will cease when all subjects on study treatment
have completed the treatment termination visit assessments as specified
in the Time and Events Schedule for Amendment 6 or by 18 January
2018, whichever occurs first. For subjects continuing treatment with
single-agent DOXIL, as per the local standard of care, only serious
adverse events should be reported to JR&D as outlined in Section 12.3.2.

Secondary Outcome(s)

Secondary end point(s): •Progression free survival rate
Time frame: up to the date of disease progression or death measured up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been
observed, whichever is later

•Objective response rate
Time frame: up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been observed, whichever is later

•Area under the concentration curve of trabectedin as derived from sparse population pharmacokinetics
Time frame = predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only

•Minimum observed plasma concentration of trabectedin as derived from sparse population pharmacokinetics
Time frame = Time frame = predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only

•Maximum observed plasma concentration of trabectedin as derived from sparse population pharmacokinetics
Time frame = Time frame = predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only

•Number of participants affected by an adverse event
Time frame = up to 30 days after the last participant has received the last dose of study medication

Timepoint(s) of evaluation of this end point: Following Amendment 6, study data collection including laboratory tests,
cardiovascular monitoring, physical examinations, tumour assessments,
PROs, and ECOG status will cease when all subjects on study treatment
have completed the treatment termination visit assessments as specified
in the Time and Events Schedule for Amendment 6 or by 18 January
2018, whichever occurs first. For subjects continuing treatment with single-agent DOXIL, as per the local standard of care, only serious adverse events should be reported to JR&D as outlined in Section 12.3.2.

Secondary ID(s)

ET743-OVC-3006

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 11/07/2013
Contact:

Results

• Results available: Yes
• Date Posted: 07/03/2019
• Date Completed: 18/01/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004808-34/results