Endometrial CarcinomaPolenNCT02506816
Preoperative Olaparib Endometrial Carcinoma Study (POLEN)
An observational study of Endometrial Carcinoma, run by MedSIR at 10 sites in Spain.
Trial summary
The primary objective of this study is to identify, in human tumour samples, biomarker changes associated to short exposure to AZD2281 as potential predictors of activity in Endometrial Carcinoma (EC). This is an exploratory study with a biological primary endpoint. Read more about this study
- Who is it for?
- Ages 18 to 90 years, women only
- Conditions the study is for
- Endometrial Carcinoma
- What is being tested?
- Olaparib
- How many people
- 36 participants
- Where
- 10 sitesSpain
- Study dates
- Feb 2016to Mar 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Patinets diagnosed with endometrial carcinoma prior surgery
Who may be able to join
- Patients must have histologically-confirmed type I primary endometrial carcinoma (EC). Diagnosis biopsy must contain 3-12 mg of tumour cellularity/stroma (Tumour: 5-20 mm) and this will be checked in the central laboratory for this trial. If tumour cellularity/stroma is inadequate, one re-biopsy with adequate tumour cellularity/stroma will be mandatory before study entry.
- WHO performance status ≤ 2.
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >10g/dL.
- Adequate liver function as shown by:
- serum bilirubin ≤ 1.5 x ULN INR < 1.3 (or < 3 on anticoagulants) ALT and AST ≤ 2.5x ULN
- Adequate renal function: serum creatinine ≤ 1.5 x mg/dL.
- Fasting serum cholesterol ≤300 mg/dL or ≤7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN.
- Signed informed consent, including consent to tissue collection and blood samples as specified by the protocol.
Who cannot join
- Subjects who have received prior anticancer therapies for the current endometrial cancer (including chemotherapy, radiotherapy, antibody based therapy, hormonotherapy or surgery).
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
- Prior treatment with any investigational drug within the preceding 4 weeks.
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior the study entry. Topical or inhaled corticosteroids are allowed.
- Patients who have received immunization with attenuated live vaccines within one week of study entry (note: during study period these kind of vaccines are also not allowed).
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Show all 11Show fewer
- Symptomatic congestive heart failure of New York heart Association Class III or IV Unstable angina pectoris, myocardial infarction within 6 months of start of study drug, Serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease Severely impaired lung function Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN Active (acute or chronic) or uncontrolled severe infections Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis A known history of HIV seropositivity.
- Patients with an active, bleeding diathesis.
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of AZD2281).
- History of noncompliance to medical regimens.
- Patients unwilling to or unable to comply with the protocol.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
MedSIR investigative site
A Coruña, 15006
MedSIR investigative site
Barcelona, 08035
MedSIR investigative site
Barcelona, 08036
MedSIR investigative site
Córdoba, 14004
MedSIR investigative site
Granollers, 08400
MedSIR
Madrid, 28034
MedSIR investigative site
Madrid, 28040
MedSIR investigative site
Santiago de Compostela, 15706
MedSIR investigative site
Valencia, 46009
MedSIR investigative site
Vigo, 36312
About this study
Official title: A Preoperative "Window-opportunity", Multicenter, Pharmacokinetic-pharmacodynamic Study to Evaluate the Inhibitory Effects of Single Agent AZD2281 (Olaparib), in Patients With Early-stage Endometrial Carcinoma
The primary objective of this study is to identify, in human tumour samples, biomarker changes associated to short exposure to AZD2281 as potential predictors of activity in Endometrial Carcinoma (EC).
This is an exploratory study with a biological primary endpoint. Clinical efficacy or safety are not a primary objective of the study.
Read the detailed description
The main objective of the present proposal study is to assess the biological consequences of PARP inhibition in type I primary EC, in patients who receive therapy with AZD2281 during the period of time between diagnosis and surgery.
This is a phase 0 trial or "Exploratory Investigational New Drug" study, a type of trial that involves limited number of patient under drug therapy and has no therapeutic or diagnostic intent because the drug exposure has a limited duration and the dosage is lower than 100% of the dose required to yield a pharmacologic effect.
The purpose of the phase 0 studies is to assist in the go versus no-go decision-making process of a drug's fate earlier in the development process, using relevant human models instead of relying on sometimes inconsistent animal data, thus helping to confirm endpoints such as mechanism of action, pharmacology, bioavailability and pharmacodynamics.
- Conditions
- Endometrial Carcinoma
- Being tested
- Olaparib
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called Lynparza
Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
| Study group | Role | What they receive |
|---|---|---|
| Olaparib | Drug exposure has a limited duration 28 (+/- 5) days. Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of Cell Cycle-related Proteins
We assessed the change from baseline in the histological score (H-score) of the cell cycle-related proteins on endometrial tumor tissues after 28 (+/- 5) days of olaparib-based therapy. In detail, expression of the cyclin D1, Ki67, and caspase-3 active proteins evaluated by an H-score according to the following formula:
H-score= 1x(%light staining) + 2x(%moderate staining) + 3x(%strong staining).
The final score ranges from 0 to 300, where 0 indicates absence of staining (corresponding to the lowest tumor proliferation rate and better outcome) and 300 the maximum staining (corresponding to the highest tumor proliferation score and worse outcome).
Measured: Baseline and Day 28 (+/- 5)
Secondary outcomes (3)
Protein Expression of Biomarkers Related to PARP-inhibition
We assessed the change from baseline in the H-score of several biomarkers targeted by olaparib-based therapy on endometrial tumor tissues after 28 (+/- 5) days of treatment. In detail, expression of protein involved in the DNA repair (PARP1, ɣH2AX), angiogenesis (VEG, HIF-1α, PTEN), apoptosis (p65, p50, p53), glucose metabolism (GLUT1), proliferation (PH3), and regulation of gene transcription (ARID1A) were evaluated by an H-score according to the following formula:
H-score= 1x(%light staining) + 2x(%moderate staining) + 3x(%strong staining).
The final score ranges from 0 to 300, where 0 indicates absence of staining and 300 the maximum staining.
Measured: Baseline and Day 28 (+/- 5)
Plasma Levels of Olaparib
Plasma concentration of olaparib administered at dosis of 300mg twice in a day (600mg/day). Values of plasma level of olaparib on days 7,14,21 and 28 were collected at time when maximum of drug concentration is reached. Data are reported as µg/mL.
Measured: Days 7,14,21 and 28
Number of Participants With Olaparib-Associated Toxicities
To assess the tolerability for all treated patients (N=36) according to NCI-CTCAE v.4.03.
Measured: Up to 28 days (+/- 5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2015 (estimated)
- Study startFeb 2016
- Primary completionJul 2018
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endometrial CarcinomaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Experior
- Responsible party
- Sponsor
- Investigators
- Antonio Llombart, MD, PhD, Study chair, Medica SIR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02506816
- Sponsor's protocol ID
- MedOPP044
- Other IDs
- 2015-001156-30, 2015
- Acronym
- Polen
- Status last verified
- Nov 2019
- First submitted
- 29 Jun 2015
- Last updated
- 30 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Preoperative "Window-opportunity", Multicenter, Pharmacokinetic-pharmacodynamic Study to Evaluate the Inhibitory Effects of Single Agent AZD2281 (Olaparib), in Patients With Early-stage Endometrial Carcinoma
- ClinicalTrials.gov ID
- NCT02506816
- Acronym / sponsor ID
- Polen / MedOPP044
- Conditions
- Endometrial Carcinoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Collaborators
- AstraZeneca, Experior
- Study start
- Feb 2016
- Primary completion
- Jul 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 23 Jul 2015 (estimated)
- Results
- Posted 15 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to identify, in human tumour samples, biomarker changes associated to short exposure to AZD2281 as potential predictors of activity in Endometrial Carcinoma (EC).
This is an exploratory study with a biological primary endpoint. Clinical efficacy or safety are not a primary objective of the study.
Detailed description
The main objective of the present proposal study is to assess the biological consequences of PARP inhibition in type I primary EC, in patients who receive therapy with AZD2281 during the period of time between diagnosis and surgery.
This is a phase 0 trial or "Exploratory Investigational New Drug" study, a type of trial that involves limited number of patient under drug therapy and has no therapeutic or diagnostic intent because the drug exposure has a limited duration and the dosage is lower than 100% of the dose required to yield a pharmacologic effect.
The purpose of the phase 0 studies is to assist in the go versus no-go decision-making process of a drug's fate earlier in the development process, using relevant human models instead of relying on sometimes inconsistent animal data, thus helping to confirm endpoints such as mechanism of action, pharmacology, bioavailability and pharmacodynamics.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib | – | Drug: OlaparibDrug exposure has a limited duration 28 (+/- 5) days. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patinets diagnosed with endometrial carcinoma prior surgery
Key inclusion criteria (8 listed)
- Patients must have histologically-confirmed type I primary endometrial carcinoma (EC). Diagnosis biopsy must contain 3-12 mg of tumour cellularity/stroma (Tumour: 5-20 mm) and this will be checked in the central laboratory for this trial. If tumour cellularity/stroma is inadequate, one re-biopsy with adequate tumour cellularity/stroma will be mandatory before study entry.
- WHO performance status ≤ 2.
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >10g/dL.
- Adequate liver function as shown by:
- serum bilirubin ≤ 1.5 x ULN INR < 1.3 (or < 3 on anticoagulants) ALT and AST ≤ 2.5x ULN
Key exclusion criteria (11 listed)
- Subjects who have received prior anticancer therapies for the current endometrial cancer (including chemotherapy, radiotherapy, antibody based therapy, hormonotherapy or surgery).
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
- Prior treatment with any investigational drug within the preceding 4 weeks.
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior the study entry. Topical or inhaled corticosteroids are allowed.
- Patients who have received immunization with attenuated live vaccines within one week of study entry (note: during study period these kind of vaccines are also not allowed).
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 |
|---|---|---|
| OlaparibAlso: LynparzaDrug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day). | Drug | Olaparib |
Primary outcome
Expression of Cell Cycle-related Proteins
Time frame: Baseline and Day 28 (+/- 5)
We assessed the change from baseline in the histological score (H-score) of the cell cycle-related proteins on endometrial tumor tissues after 28 (+/- 5) days of olaparib-based therapy. In detail, expression of the cyclin D1, Ki67, and caspase-3 active proteins evaluated by an H-score according to the following formula: H-score= 1x(%light staining) + 2x(%moderate staining) + 3x(%strong staining). The final score ranges from 0 to 300, where 0 indicates absence of staining (corresponding to the lowest tumor proliferation rate and better outcome) and 300 the maximum staining (corresponding to the highest tumor proliferation score and worse outcome).
3 secondary outcomes
Protein Expression of Biomarkers Related to PARP-inhibition
Time frame: Baseline and Day 28 (+/- 5)
Plasma Levels of Olaparib
Time frame: Days 7,14,21 and 28
Number of Participants With Olaparib-Associated Toxicities
Time frame: Up to 28 days (+/- 5)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Antonio Llombart, MD, PhD study chair
Medica SIR
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Endometrial Carcinoma, run by MedSIR at 10 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 8 inclusion and 11 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 30 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Expression of Cell Cycle-related Proteins (time frame: Baseline and Day 28 (+/- 5)). 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 30 Nov 2020.