Endometrial NeoplasmsPhase 2DOMECNCT03951415
Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer
A Phase 2 study testing PARP inhibitor and Anti-PD-L1 in people with Endometrial Neoplasms and Uterine Neoplasms, run by Leiden University Medical Center at 8 sites in Netherlands.
Trial summary
The DOMEC trial is designed as a Dutch Gynecological Oncology Group (DGOG), prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer or carcinosarcoma of the uterus to investigate the efficacy of the combination therapy of olaparib tablets and… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Neoplasms, Uterine Neoplasms, Endometrium Cancer
- What is being tested?
- PARP inhibitor and Anti-PD-L1
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 8 sitesNetherlands
- Study dates
- 8 Jul 2019to 1 Aug 2021
- 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
- Written informed consent
- Age > 18 years old
- Histologically confirmed diagnosis of endometrial cancer or carcinosarcoma of the endometrium.
- Metastatic disease or locally advanced tumor not amenable to local therapy.
- Documented progressive disease before enrolment.
- Measurable lesions outside irradiated field or progressive measurable lesions in irradiated area
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- Not eligible for hormonal therapy (because of negative hormone receptor/poor differentiation, or after failure of hormonal therapy).
- Previous failure of chemotherapy, or refusal to undergo chemotherapy or chemo-naive patients not suitable for chemotherapy.
- WHO performance 0-1
- Adequate organ system function as 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) (not applicable to Gilbert's syndrome)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN unless liver metastases are present in which case they must be ≤ 5x ULN
- Patients must have creatinine clearance estimated of ≥51 mL/min estimated using the Cockcroft-Gault equation or 24 hr urine clearance.
- Life expectancy of at least 16 weeks.
- Measurable disease as defined by RECIST 1.1 criteria
- Able to swallow and retain oral medication.
- A female is eligible to enter and participate in this study if there is:
Who cannot join
- Participation in another clinical study with an investigational product during the last month or previous enrolment in the present study.
- Any previous treatment with PARP inhibitor, including olaparib and/or any previous treatment with a PD1 or PD-L1 inhibitor
- History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence or adequately treated non-melanoma skin cancer, lentigo maligna or carcinoma in situ.
- History of leptomeningeal carcinomatosis, symptomatic uncontrolled brain metastases (≤2mg/ day corticosteroids started ≥4 weeks prior to treatment is accepted) and spinal cord compression (unless received definitive treatment and clinically stable for 28 days) .
- 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 or moderate CYP3A inhibitors and inducers.
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- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (except intranasal and inhaled corticosteroids or systemic prednisone ≤ 10 mg/day)
- Major surgery ≤2 weeks of starting study treatment
- History of active primary immunodeficiency
- Active or prior documented autoimmune or inflammatory disorders, with exception of: vitiligo or alopecia, hypothyroidism stable on hormone replacement, any chronic skin condition that does not require systemic therapy, celiac disease controlled by diet alone
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- Active infection including tuberculosis, hepatitis B/C and HIV
- Patients with an expected or known hypersensitivity to olaparib or durvalumab or any of the excipients of the products.
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
- Pregnancy or breastfeeding
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Netherlands8 sites
Amsterdam UMC, AMC
Amsterdam, 1105 AZ
NKI-AVL
Amsterdam
Universitair Medisch Centrum Groningen
Groningen
Leiden University Medical Center
Leiden, 2300RC
Academisch Ziekenhuis Maastricht
Maastricht
RadboudMC
Nijmegen
Erasmus MC
Rotterdam
Universitair Medisch Centrum Utrecht
Utrecht
About this study
The DOMEC trial is designed as a Dutch Gynecological Oncology Group (DGOG), prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer or carcinosarcoma of the uterus to investigate the efficacy of the combination therapy of olaparib tablets and durvalumab IV.
Read the detailed description
The prognosis of recurrent or persistent endometrial carcinoma not amenable to local therapy is poor. First line therapy exists of platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been described.The combination of Poly(ADP-ribose) polymerases (PARP) inhibition and Programmed death-ligand 1 (PD-L1) blocking has great potential in the treatment of recurrent endometrial cancer. The DOMEC trial is designed to investigate this treatment combination among all molecular subgroups.
The DOMEC trial is designed as a DGOG, prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer, including carcinosarcoma of the uterus. Patients must have had one prior platinum-based chemotherapeutic regimen or not be able/willing to get chemotherapy. The aim is to investigate the efficacy of the combination therapy of olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks in terms of progression free survival. Secondary objectives are to investigate objective response rate, overall survival, safety and predictive biomarkers.
- Conditions
- Endometrial Neoplasms, Uterine Neoplasms, Endometrium Cancer
- Being tested
- PARP inhibitor and Anti-PD-L1
- Keywords
- Poly (ADP-ribose) Polymerase Inhibitors, Antibodies, Monoclonal, Checkpoint Inhibitors, olaparib, durvalumab, Anti-PD-L1
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PARP inhibitor and Anti-PD-L1Drug
Also called olaparib, durvalumab, PARP inhibitor, Anti-PD-L1 Monoclonal Antibody
olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| PARP inhibitor and Anti-PD-L1 | Experimental | olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks Receives: Drug: PARP inhibitor and Anti-PD-L1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
PFS will be counted from the date of registration until the first observation of radiological progressive disease according to RECIST 1.1 criteria or death due to any cause, whichever occurred first.
Measured: 6 months
Secondary outcomes (4)
Objective response rate (ORR)
according to RECIST 1.1 criteria
Measured: 12 weeks
Overall survival (OS)
OS will be determined from the date of registration until death from any cause.
Measured: Through study completion, up to 36 months
Adverse events
Assessed by NCI Common Terminology Criteria for adverse Events (CTCAE) version 5.0
Measured: Through study completion, up to 36 months
Predictive biomarkers in tumor biopsy
MMRd/POLE, HR status, quantification of CD3,CD4,CD8,CD103,CD161,PD-1,LAG3,CTLA-4,NKG2A,GOXp3 positieve T cells, NK cells, percentage PD-L1 on myeloid cells/tumorcells, quantification of myeloid cell infiltration (CD68,CD14,CD33,CD163) in tumor biopsies.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start8 Jul 2019
- Primary completion1 Aug 2021 (estimated)
- Study completion1 Aug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial NeoplasmsStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam University Medical Center, Erasmus Medical Center, Maastricht University Medical Center, The Netherlands Cancer Institute, Radboud University Medical Center, University Medical Center Groningen, UMC Utrecht, AstraZeneca
- Responsible party
- Principal investigator, J.R. Kroep, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951415
- Sponsor's protocol ID
- DOMEC
- Acronym
- DOMEC
- Status last verified
- Mar 2021
- First submitted
- 30 Apr 2019
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer
- ClinicalTrials.gov ID
- NCT03951415
- Acronym / sponsor ID
- DOMEC / DOMEC
- Conditions
- Endometrial Neoplasms, Uterine Neoplasms, Endometrium Cancer
- Keywords
- Poly (ADP-ribose) Polymerase Inhibitors, Antibodies, Monoclonal, Checkpoint Inhibitors, olaparib, durvalumab, Anti-PD-L1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Amsterdam University Medical Center, Erasmus Medical Center, Maastricht University Medical Center, The Netherlands Cancer Institute, Radboud University Medical Center, University Medical Center Groningen, UMC Utrecht, AstraZeneca
- Study start
- 8 Jul 2019 (actual)
- Primary completion
- 1 Aug 2021 (estimated)
- Study completion
- 1 Aug 2021 (estimated)
- First posted
- 15 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The DOMEC trial is designed as a Dutch Gynecological Oncology Group (DGOG), prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer or carcinosarcoma of the uterus to investigate the efficacy of the combination therapy of olaparib tablets and durvalumab IV.
Detailed description
The prognosis of recurrent or persistent endometrial carcinoma not amenable to local therapy is poor. First line therapy exists of platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been described.The combination of Poly(ADP-ribose) polymerases (PARP) inhibition and Programmed death-ligand 1 (PD-L1) blocking has great potential in the treatment of recurrent endometrial cancer. The DOMEC trial is designed to investigate this treatment combination among all molecular subgroups.
The DOMEC trial is designed as a DGOG, prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer, including carcinosarcoma of the uterus. Patients must have had one prior platinum-based chemotherapeutic regimen or not be able/willing to get chemotherapy. The aim is to investigate the efficacy of the combination therapy of olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks in terms of progression free survival. Secondary objectives are to investigate objective response rate, overall survival, safety and predictive biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PARP inhibitor and Anti-PD-L1 | Experimental | Drug: PARP inhibitor and Anti-PD-L1olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Written informed consent
- Age > 18 years old
- Histologically confirmed diagnosis of endometrial cancer or carcinosarcoma of the endometrium.
- Metastatic disease or locally advanced tumor not amenable to local therapy.
- Documented progressive disease before enrolment.
Key exclusion criteria (17 listed)
- Participation in another clinical study with an investigational product during the last month or previous enrolment in the present study.
- Any previous treatment with PARP inhibitor, including olaparib and/or any previous treatment with a PD1 or PD-L1 inhibitor
- History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence or adequately treated non-melanoma skin cancer, lentigo maligna or carcinoma in situ.
- History of leptomeningeal carcinomatosis, symptomatic uncontrolled brain metastases (≤2mg/ day corticosteroids started ≥4 weeks prior to treatment is accepted) and spinal cord compression (unless received definitive treatment and clinically stable for 28 days) .
- Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PARP inhibitor and Anti-PD-L1Also: olaparib, durvalumab, PARP inhibitor, Anti-PD-L1 Monoclonal Antibodyolaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks | Drug | PARP inhibitor and Anti-PD-L1 |
Primary outcome
Progression free survival (PFS)
Time frame: 6 months
PFS will be counted from the date of registration until the first observation of radiological progressive disease according to RECIST 1.1 criteria or death due to any cause, whichever occurred first.
4 secondary outcomes
Objective response rate (ORR)
Time frame: 12 weeks
Overall survival (OS)
Time frame: Through study completion, up to 36 months
Adverse events
Time frame: Through study completion, up to 36 months
Predictive biomarkers in tumor biopsy
Time frame: At baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PARP inhibitor and Anti-PD-L1 in people with Endometrial Neoplasms and Uterine Neoplasms, run by Leiden University Medical Center at 8 sites in Netherlands.
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 20 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands. 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?
Results are not available in the source record.
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: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2021.