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Ovarian CancerPhase 2NCT03470805

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

A Phase 2 study testing Olaparib in people with Ovarian Cancer, run by Grupo Español de Investigación en Cáncer de Ovario at 16 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
Olaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
16 sitesSpain
Study dates
21 Jun 2018to 27 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Last CT prior to the inclusion in the trial must be trabectedin + PLD. Patients must have received at least 4 cycles of treatment, and have reached a partial or complete response, assessed by RECIST 1.1 criteria and no evidence of a rising CA 125, following the chemotherapy course.
  • 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.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing if sBRCA analysis is not available at study site. If there is not written confirmation of the availability of an archived tumour sample or gBRCA test performed prior to enrolment the patient is not eligible for the study.
  • For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfil the following criteria:
  • Provision of informed consent for genetic research
  • Provision of informed consent for biomarker research

Who cannot join

  • 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.
  • Rising CA125 after chemotherapy is finished until inclusion. Pre-treatment CA-125 measurements must meet criterion specified below:
  • 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.
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  • 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.
  • Breast feeding women.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Patients with known active hepatitis (i.e. Hepatitis B or C).
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Spain16 sites

  • ICO Badalona

    Badalona

  • H Reina Sofía Cordoba

    Córdoba, 14004

  • Hospital de Guadalajara

    Guadalajara

  • Complejo Hospitalario de Jaen

    Jaén

  • Hospital de Jerez de la Frontera

    Jerez de la Frontera

  • Hospital Lucus Augusti

    Lugo

  • Hospital Universitario La Paz

    Madrid, 28046

  • Fundación Jimenez Diaz

    Madrid

  • Hospital Ramon y Cajal

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Puerta de Hierro

    Madrid

  • Hospital Clinico Universitario Virgen Arrixaca

    Murcia

  • Hospital Universitario de Valdecilla

    Santander, 39008

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital Virgen Macarena

    Seville

  • Instituto Valenciano de Oncología

    Valencia, 46009

Other trials in Spain

About this study

Official title: Phase-II Study of Olaparib as Maintenance Therapy After Response to Trabectedin-pegylated Liposomal Doxorubicin in Recurrent Ovarian Carcinoma

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".

Read more

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
Being tested
Olaparib
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaparibDrug

    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

Study groups in NCT03470805
Study groupRoleWhat they receive
OlaparibExperimentalOlaparib orally twice daily at 150 mgs bid continually
Receives: Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 24 months

Secondary outcomes (4)

  1. Time to First Subsequent Treatment (TFST)

    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

    Measured: Up to 24 months

  2. Time to Second Subsequent Treatment (TSST)

    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.

    Measured: Up to 24 months

  3. Progression free survival 2 (PFS2)

    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

    Measured: Up to 24 months

  4. Incidence of Treatment Adverse Events

    Number of Adverse Events per patient

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2018
  2. Study start21 Jun 2018
  3. Primary completion27 Jul 2022
  4. Study completion27 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Olaparib as maintenance therapy
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03470805
Sponsor's protocol ID
OLATRA
Other IDs
2017-003183-13, 2017
Status last verified
Sep 2022
First submitted
28 Feb 2018
Last updated
23 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib in people with Ovarian Cancer, run by Grupo Español de Investigación en Cáncer de Ovario at 16 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03470805.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.

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