Rechallenge with Pegylated Liposomal Doxorubicin Added to Trabectedin in Recurrent Ovarian Cancer: a Multicenter, Prospective Trial.(Reprab Study- Mito 36)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Jul 2021 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pharma Mar S.A

External identifiers

EU CT number

2024-518847-40-00

EudraCT number

2017-004690-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate that rechallenge with pegylated liposomal doxorubicin (PLD) with the combination of trabectedin (Yondelis®) is active (objective response rate) in relapsed ovarian cancer patients who have already received pegylated liposomal doxorubicin and progress within 6-12 months after the end of last platinum or in fully platinum sensitive patients not able to receive or not willing to receive other platinum treatments

Secondary objectives 7

1. Translational end point*: to define the correlation between genetic assessment, including BRCA1/2 genes, and Epithelial ovarian cancer (EOC) treatment and prognosis and to investigate how genetic pattern evolves over treatments
2. To analyze safety profile, progression free survival (PFS), overall survival (OS), following retreatment with trabectedin and PLD
3. To evaluate the time from enrollment to subsequent chemotherapy and the overall survival counted from the administration of subsequent chemotherapy
4. Duration of Response
5. Clinical benefit rate at 24 weeks
6. To evaluate serological response of CA-125
7. To analyze the quality of life (QoL) 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)

Conditions and MedDRA coding

recurrent ovarian cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Female aged ≥ 18 years
2. Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
3. Partially platinum sensitive patients or fully platinum sensitive patients not able to receive or not willing to receive other platinum treatments, who have previously received PLD (carboplatin-pegylated liposomal doxorubicin or pegylated liposomal doxorubicin alone)
4. ECOG PS 0-1
5. Subject has radiographically-documented measurable disease, as per RECIST 1.1 at study entry (CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression)
6. Be able to receive IV dexamethasone or an equivalent IV corticosteroid
7. Have all of the following: - hemoglobin ≥9 g/dL (without transfusion in the prior 7 days). Subjects may be enrolled into the study while receiving recombinant erythropoietin provided they have received recombinant; erythropoietin for at least 4 weeks before the first dose of study drug; albumin > 25 g/L; absolute neutrophil count (ANC) >1,500/μL; platelet count >100,000/μL (without transfusion in the prior 7 days); either a serum creatinine <=1.5 mg/dL or a calculated glomerular filtration rate >60 mL/min/1.73 m2 (Cockcroft-Gault); CPK <2.5 x upper limit of normal (ULN)
8. Have total bilirubin 1,5xULN, measure direct and indirect bilirubin to evaluate for Gilbert’s syndrome (if direct bilirubin is within normal range, subject may be eligible)
9. Have alkaline phosphatase (ALP) ≤ 2.5xULN; if the ALP is >2.5xULN, then an ALP liver fraction or 5' nucleotidase must be
10. Have AST and ALT ≤ 2.5xULN
11. Have LVEF by MUGA scan or 2D-ECHO within normal limits for the institution
12. Patients must be in postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically
13. Evidence of not pregnancy status as documented by a negative beta-human chorionic gonadotropin (ß-hCG) test
14. Not breastfeeding women
15. Adequate recovery from acute toxicity of any prior treatment

Exclusion criteria 19

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 from the last dose of platinum
3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
4. Known hypersensitivity to any of the components of PLD or trabectedin i.v. formulation
5. Previous treatment with Trabectedin
6. Known hypersensitivity to dexamethasone
7. Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy.
8. History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer
9. Myocardial failure within six months before enrolment, New York Heart Association (NYHA) Class II or worse heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
10. Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential subjects who test positive for hepatitis B surface antigen or hepatitis C antibodies are allowed provided they do not have active disease requiring antiviral therapy). Also known history of liver carcinoma and cholangitis with abnormal liver functionality
11. 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
12. Breastfeeding women
13. Pregnant women
14. Known clinically relevant CNS metastases
15. Psychiatric disorder that prevents compliance with protocol
16. Patients with concurrent serious or uncontrolled infection
17. Patients in need of yellow fever vaccine while on study chemotherapy
18. Active infection
19. Any other unstable medical condition

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response and progression will be evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Anna Fagotti

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Anna Fagotti

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications