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Preoperative Olaparib Endometrial Carcinoma Study (POLEN) (Polen)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02506816
Recruitment Status : Completed
First Posted : July 23, 2015
Results First Posted : November 15, 2019
Last Update Posted : December 19, 2019
Sponsor:
Collaborators:
AstraZeneca
Experior
Information provided by (Responsible Party):
MedSIR

Brief 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. Clinical efficacy or safety are not a primary objective of the study.


Condition or disease Intervention/treatment
Endometrial Carcinoma Drug: Olaparib

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.

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Study Type : Observational
Actual Enrollment : 36 participants
Observational Model: Case-Only
Time Perspective: Prospective
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
Study Start Date : February 2016
Actual Primary Completion Date : July 2018
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Group/Cohort Intervention/treatment
Olaparib
Drug exposure has a limited duration 28 (+/- 5) days.
Drug: Olaparib
Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Other Name: Lynparza




Primary Outcome Measures :
  1. 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).



Secondary Outcome Measures :
  1. Protein Expression of Biomarkers Related to PARP-inhibition [ Time Frame: Baseline and Day 28 (+/- 5) ]

    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.


  2. Plasma Levels of Olaparib [ Time Frame: Days 7,14,21 and 28 ]
    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.

  3. Number of Participants With Olaparib-Associated Toxicities [ Time Frame: Up to 28 days (+/- 5) ]
    To assess the tolerability for all treated patients (N=36) according to NCI-CTCAE v.4.03.


Biospecimen Retention:   Samples With DNA
Tumor cells Plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patinets diagnosed with endometrial carcinoma prior surgery
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

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.

Information from the National Library of Medicine

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): NCT02506816


Locations
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Spain
MedSIR investigative site
Barcelona, Spain, 08035
MedSIR investigative site
Barcelona, Spain, 08036
MedSIR investigative site
Cordoba, Spain, 14004
MedSIR investigative site
Coruña, Spain, 15006
MedSIR investigative site
Granollers, Spain, 08400
MedSIR
Madrid, Spain, 28034
MedSIR investigative site
Madrid, Spain, 28040
MedSIR investigative site
Santiago De Compostela, Spain, 15706
MedSIR investigative site
Valencia, Spain, 46009
MedSIR investigative site
Vigo, Spain, 36312
Sponsors and Collaborators
MedSIR
AstraZeneca
Experior
Investigators
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Study Chair: Antonio Llombart, MD, PhD Medica SIR
  Study Documents (Full-Text)

Documents provided by MedSIR:
Study Protocol  [PDF] November 3, 2016
Statistical Analysis Plan  [PDF] December 11, 2017

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Responsible Party: MedSIR
ClinicalTrials.gov Identifier: NCT02506816    
Other Study ID Numbers: MedOPP044
First Posted: July 23, 2015    Key Record Dates
Results First Posted: November 15, 2019
Last Update Posted: December 19, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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Carcinoma
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents