Olaparib After Response to Trabectedin-pegylated Liposomal Doxorubicin in Recurrent Ovarian Carcinoma
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|ClinicalTrials.gov Identifier: NCT03470805|
Recruitment Status : Active, not recruiting
First Posted : March 20, 2018
Last Update Posted : October 10, 2019
Epithelial ovarian cancer harbours 20% Breast Cancer gene (BRCA)1/2 mutations independently of family history. Poly ADP ribose polymerase (PARP) inhibitors (PARPi) have shown clinical activity among patients with homologous recombination deficiency (HRD) and specifically among BRCA1/2 mutation carriers.
The European Medicines Agency (EMA) approved the use of olaparib as maintenance therapy "as monotherapy for the maintenance treatment of adult patients with platinum sensitive relapsed BRCA mutated (germline and/or somatic) high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy".
Trabectedin and Pegylated liposomal doxorubicin (PLD) have shown relevant activity in relapsed epithelial ovarian cancer. In the relapse with Treatment-free interval of last platinum (TFIp) between 6 and 12 months this efficacy translated into an increase in Overall survival (OS) and Progression free survival (PFS).
There is an increase of hypersensitivity reactions (HSR) among platinum sensitive patients, that reaches 44% in third line and does not always allow for platinum use despite desensitization protocols. In relapse with TFIp between 6-12 months the use of Trabectedin+PLD is accepted in guidelines and consensus.
Following clinical BRCAness criteria a group of patients that harbours up to 50% of BRCA1/2 mutations can be selected. Olaparib has been licensed according to EMA for maintenance in BRCA mutated patients after response to platinum following Study 19 phase II trial and further confirmed with phase III SOLO-2 data. However there is no evidence of the benefit of adding olaparib after Trabectedin+PLD response among BRCA1/2 carriers.
The combination of Trabectedin+PLD, as well as both single drugs, have shown higher activity among BRCA1/2 carriers.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer||Drug: Olaparib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Olaparib as maintenance therapy|
|Masking:||None (Open Label)|
|Official Title:||Phase-II Study of Olaparib as Maintenance Therapy After Response to Trabectedin-pegylated Liposomal Doxorubicin in Recurrent Ovarian Carcinoma|
|Actual Study Start Date :||June 21, 2018|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
Olaparib orally twice daily at 150 mgs bid continually
Olaparib will be dispensed to patients on Day 1 and every 28 days thereafter until disease progression, unacceptable toxicity, withdraws from the study or closure of the study
- Progression free survival (PFS) [ Time Frame: Up to 24 months ]Time from date of first olaparib dose until the date of objective radiological disease progression according to modified RECIST 1.1 or death (by any cause in the absence of progression).
- Time to First Subsequent Treatment (TFST) [ Time Frame: Up to 24 months ]Time from date of first olaparib dose (treatment initiation) to date of first subsequent treatment commencement or death due to any cause if this occurs before commencement of first subsequent treatment
- Time to Second Subsequent Treatment (TSST) [ Time Frame: Up to 24 months ]Time from date of first olaparib dose (treatment initiation) to date of second subsequent treatment commencement or death due to any cause if this occurs before commencement of second subsequent treatment.
- Progression free survival 2 (PFS2) [ Time Frame: Up to 24 months ]Interval from the first olaparib dose (treatment initiation) to the earliest of the progression events subsequent to that used for the primary variable PFS, or death
- Incidence of Treatment Adverse Events [ Time Frame: Up to 24 months ]Number of Adverse Events per patient
- Predictive biomarkers of long PFS [ Time Frame: Up to 24 months ]Gene Mutations
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): NCT03470805
|H Reina Sofía Cordoba|
|Cordoba, Spain, 14004|
|Hospital de Guadalajara|
|Complejo Hospitalario de Jaen|
|Hospital de Jerez de la Frontera|
|Jerez De La Frontera, Spain|
|Hospital Lucus Augusti|
|Hospital Universitario La Paz|
|Madrid, Spain, 28046|
|Fundación Jimenez Diaz|
|Hospital Ramon y Cajal|
|Hospital Universitario 12 de Octubre|
|Hospital Universitario Puerta de Hierro|
|Hospital Clinico Universitario Virgen Arrixaca|
|Hospital Universitario de Valdecilla|
|Santander, Spain, 39008|
|Hospital Universitario Virgen del Rocío|
|Hospital Virgen Macarena|
|Instituto Valenciano de Oncología|
|Valencia, Spain, 46009|
|Principal Investigator:||Andres Redondo, MD||Hospital La Paz|
|Principal Investigator:||Ignacio Romero, MD||Fundacion Instituto Valenciano de Oncologia|