Olaparib After Response to Trabectedin-pegylated Liposomal Doxorubicin in Recurrent Ovarian Carcinoma

NCT03470805 | Completed Phase 2

• 2 other identifiers: OLATRA2017-003183-13
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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).

  Up to 24 months

Secondary Outcomes (4)

• Time to First Subsequent Treatment (TFST)

  Up to 24 months

• Time to Second Subsequent Treatment (TSST)

  Up to 24 months

• Progression free survival 2 (PFS2)

  Up to 24 months

• Incidence of Treatment Adverse Events

  Up to 24 months

Other Outcomes (1)

• Predictive biomarkers of long PFS

  Up to 24 months

Study Arms (1)

Olaparib

EXPERIMENTAL

Olaparib orally twice daily at 150 mgs bid continually

Drug: Olaparib

Interventions

Olaparib DRUG

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

Olaparib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Female aged ≥18 years.
• Patients with high-grade serous or endometrioid ovarian carcinoma.
• Treatment-free interval of last platinum (TFIp) higher than 6 months.
• BRCA1/2 germline or somatic deleterious mutation.
• Patient must have received two or more previous chemotherapy (CT) regimens, including first line platinum based CT and last trabectedin + PLD. There is no limit of previous number of CT lines.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy ≥ 16 weeks.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
• Any previous treatment with PARP inhibitor.
• If the first value is within upper limit of normal (ULN) the patient is eligible to be randomised and a second sample is not required.
• If the first value is greater than ULN a second assessment must be performed at least 7 days after the first. If the second assessment is ≥ 15% more than the first, the patient is not eligible.
• Other malignancy within the last 3 years except: adequately treated non-melanoma skin cancer, curatively treated cervical carcinoma in situ, breast carcinoma in situ, and grade 1 endometrial carcinoma in stage 1.
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St Johns Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Persistent toxicities (\> Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of these diseases.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment.
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a poor medical condition due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.

Sponsors & Collaborators

• Grupo Español de Investigación en Cáncer de Ovario: lead
• AstraZeneca: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (16)

ICO Badalona

Badalona, Spain

Location

H Reina Sofía Cordoba

Córdoba, 14004, Spain

Location

Hospital de Guadalajara

Guadalajara, Spain

Location

Complejo Hospitalario de Jaen

Jaén, Spain

Location

Hospital de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Hospital Lucus Augusti

Lugo, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Fundación Jimenez Diaz

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Clinico Universitario Virgen Arrixaca

Murcia, Spain

Location

Hospital Universitario de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Virgen Macarena

Seville, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Andres Redondo, MD

  Hospital La Paz

  PRINCIPAL INVESTIGATOR

• Ignacio Romero, MD

  Fundacion Instituto Valenciano de Oncologia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Olaparib as maintenance therapy

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 20, 2018
• Study Start: June 21, 2018
• Primary Completion: July 27, 2022
• Study Completion: July 27, 2022
• Last Updated: September 23, 2022

Record last verified: 2022-09

Locations

ES (16)