Condition category
Cancer
Date applied
31/10/2011
Date assigned
31/10/2011
Last edited
21/09/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Miss Sam Ballantyne

ORCID ID

Contact details

Guy's and St Thomas' Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
-
samb@oclinical.com

Additional identifiers

EudraCT number

2010-022949-17

ClinicalTrials.gov number

Protocol/serial number

10836

Study information

Scientific title

Phase III international, randomized study of Trabectedin plus Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin plus PLD in patients with ovarian cancer progressing within 6-12 months of last platinum

Acronym

Study hypothesis

No data are available comparing trabectedin + PLD to a platinum-based regimen. Based on data from OVA-301 and CALYPSO the proposed INOVATYON trial will investigate the role of a non-platinum combination for the treatment of ovarian cancer patients relapsing between six and 12 months after last platinum-based chemotherapy
1. Does the combination of trabectedin and PLD prolong overall survival over carboplatin + PLD?
2. Progression Free Survival, response rate, safety profile, quality of life,Time from randomization to subsequent chemotherapy, response rate and progression free survival after subsequent therapies, overall survival counted from the administration of subsequent chemotherapy

Sub study (Italy Only)
Pharmacokinetic analyses in plasma and ascites in a subset of patients receiving trabectedin and PLD
1. To demonstrate that the combination of trabectedin (Yondelis®) and pegylated liposomal doxorubicin (PLD) prolongs overall survival (OS) over carboplatin and PLD in patients with relapsed ovarian cancer progressing within 6-12 months after end of last platinum.
2. To evaluate the time from randomization to subsequent chemotherapy and the overall survival counted from the administration of subsequent chemotherapy.
2.1. To evaluate serological response of CA-125 in each arm.
2.2. To compare the quality of life (QoL) in each arm using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (QLQ-C30) and the Quality of Life Questionnaire-OV28 (QLQ-OV28).
2.3. To compare safety profile, progression free survival (PFS), objective response rate (ORR), the type and length of remission (response rate and PFS) after subsequent therapies following each of the two combinations.
2.4. Sub-study in selected centers (ITALY ONLY): To perform pharmacokinetic (PK) analyses in both plasma and ascites in a subset of patients receiving trabectedin and PLD

Ethics approval

First MREC, 04/10/2011, ref: 11/LO/1261

Study design

Randomised interventional treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Gynaecological cancer, ovarian cancer

Intervention

Yondelis & PLD versus Carboplatin & PLD

Patients are either given trabectedin (Yondelis®) and pegylated liposomal doxorubicin (PLD) or carboplatin and PLD

Intervention type

Drug

Phase

Phase III

Drug names

Carboplatin, Pegylated Liposomal Doxorubicin (PLD), Trabectedin (Yondelis®)

Primary outcome measures

Demonstrate that the combination of trabectedin (Yondelis®) and pegylated liposomal doxorubicin

Secondary outcome measures

1. CA-125 response
2. To evaluate serological response of CA-125 in each arm
3. Quality of life
4. To compare the quality of life (QoL) in each arm using the European Organization for Research
5. Safety Profile
6. To compare safety profile, progression free survival (PFS), objective response rate (ORR)

Sub study (Italy only):
1. To perform pharmacokinetic (PK) analyses in both plasma
2. Time to subsequent chemotherapy
3. To evaluate the time from randomization to subsequent chemotherapy and the overall survival counted

Overall trial start date

01/05/2011

Overall trial end date

01/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Female, aged = 18 years
2. Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer
3. Progression-free interval between six and twelve (6-12) months (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmation through radiologic imagery). Patients may have received up to two platinum-based chemotherapy lines, of which at least one must have contained a taxane
4. Measurable or evaluable disease confirmed by radiological imaging, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET/CT scan at study entry. CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression) or histological proven recurrent ovarian cancer even in the absence of postoperatively measurable or evaluable lesions
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2
6. Estimated life expectancy = 12 weeks
7. Patients must be accessible for treatment and follow-up
8. Adequate organ function within 14 days prior to first cycle as evidenced by:
8.1. Peripheral blood counts and serum chemistry values:
8.1.1. Hemoglobin ³ 9 g/dl
8.1.2. Absolute neutrophil count (ANC) ³ 1,500/ml
8.1.3. Platelet count ³ 100,000/ml
8.1.4. Estimated glomerular filtration rate > 60 ml/min according to the Cockroft-Gault formula
8.1.5. Creatine phosphokinase (CPK) = 2.5 x ULN
8.2. Hepatic function variables:
8.2.1. Total bilirubinULN
8.2.2. Total alkaline phosphatase 2.5 ULN (consider hepatic isoenzymes 5-nucleotidase if the elevation could be osseous in origin)
8.2.3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be £ 2.5 x ULN
9. Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD
10. Informed consent of the patient

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 588. 442 events and about 588 patients are needed

Participant exclusion criteria

1. Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors)
2. Patients who did not respond to last platinum-based therapy or in whom last relapse occurred < 6 months or > 12 months from the last dose of platinum
3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
4. Pre-existing grade > 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0
5. Myocardial infarct within six months before enrolment, New YorkHeart Association (NYHA) Class II or worse heart failure, uncontrolled angina, severe uncontrolled ventricular arrythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
6. History of liver disease
7. Concurrent severe medical problems or any unstable medical condition unrelated to malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
8. Breastfeeding women and women of child bearing potential must use effective contraception during treatment and 3 months thereafter, which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to patients that are surgically sterile)
9. Prior exposure to trabectedin
10. Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending
11. Prior severe PLD related toxicity
12. Prior exposure to cumulative doses of doxorubicin >400mg/m2 or epirubicin >720mg/m2
13. Treatment with any investigational product within 30 days prior to inclusion in the study
14. Patients with known hypersensitivity to Trabectedin and any of its excipients or yellow fever vaccine
15. Patients with concurrent serious or uncontrolled infection
16. Patients in need of yellow fever vaccine while on study chemotherapy

Recruitment start date

01/05/2011

Recruitment end date

01/12/2013

Locations

Countries of recruitment

Denmark, Finland, Germany, Italy, Spain, United Kingdom

Trial participating centre

Guy's and St Thomas' Hospital
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

Mario Negri Gynecological Oncology Group - MaNGO (Italy)

Sponsor details

[Istituto di Ricerche Farmacologiche "Mario Negri"]
Via La Masa
Milano
19 - 20156
Italy

Sponsor type

Research organisation

Website

http://www.marionegri.it/mn/en/index.html

Funders

Funder type

Industry

Funder name

Pharma Mar (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

21/09/2016: Verifying study status with principal investigator.