Clinical trial NCT02506816: Preoperative Olaparib Endometrial Carcinoma Study (POLEN)
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Endometrial Carcinoma
Lead sponsor: MedSIR
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Experior
First posted: 2015-07-23
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patinets diagnosed with endometrial carcinoma prior surgery

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.

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.

Eligibility 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.

Primary outcomes:
measure: Expression of Cell Cycle-related Proteins
timeFrame: Baseline and Day 28 (+/- 5)
Secondary outcomes:
measure: Protein Expression of Biomarkers Related to PARP-inhibition
timeFrame: Baseline and Day 28 (+/- 5)
measure: Plasma Levels of Olaparib
timeFrame: Days 7,14,21 and 28
measure: Number of Participants With Olaparib-Associated Toxicities
timeFrame: Up to 28 days (+/- 5)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: MedSIR investigative site
city: Barcelona
country: Spain
facility: MedSIR investigative site
city: Cordoba
country: Spain
facility: MedSIR investigative site
city: Coruña
country: Spain
facility: MedSIR investigative site
city: Granollers
country: Spain
facility: MedSIR investigative site
city: Madrid
country: Spain
facility: MedSIR
city: Madrid
country: Spain
facility: MedSIR investigative site
city: Santiago De Compostela
country: Spain
facility: MedSIR investigative site
city: Valencia
country: Spain
facility: MedSIR investigative site
city: Vigo
country: Spain
facility: MedSIR investigative site
Study officials:
affiliation: Medica SIR
name: Antonio Llombart, MD, PhD
role: STUDY_CHAIR
References: