Trial Outcomes & Findings for Preoperative Olaparib Endometrial Carcinoma Study (POLEN) (NCT NCT02506816)

Last Updated: 2020-11-30

Results Overview

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).

Recruitment status

COMPLETED

Target enrollment

36 participants

Primary outcome timeframe

Baseline and Day 28 (+/- 5)

Results posted on

2020-11-30

Participant Flow

Out of 49 patients initially considered for study eligibility, 9 did not sign the ICF and 4 did not meet eligibility criteria (screen failures). Out of 36 patients who were treated and included in the overall analysis and safety, 5 were excluded from the primary and secondary analysis because of no valid samples for biomarker characterization.

Participant milestones

Participant milestones
Measure	Olaparib Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Overall Study STARTED	36
Overall Study Samples Availability	31
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaparib Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Overall Study Adverse Event	3

Baseline Characteristics

13 Screening Failures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaparib n=36 Participants Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Age, Categorical <=18 years	0 Participants n=5 Participants • 13 Screening Failures
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants • 13 Screening Failures
Age, Categorical >=65 years	17 Participants n=5 Participants • 13 Screening Failures
Sex: Female, Male Female	36 Participants n=5 Participants • 13 Screening Failures
Sex: Female, Male Male	0 Participants n=5 Participants • 13 Screening Failures
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Spain	36 participants n=5 Participants • 13 Screening Failures

PRIMARY outcome

Timeframe: Baseline and Day 28 (+/- 5)

Population: The analysis was performed in the complete population of analysis (N = 36) and in the population of biomarkers (N = 31).

Outcome measures

Outcome measures
Measure	Olaparib n=31 Participants Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Expression of Cell Cycle-related Proteins Cyclin D1 pre-treatment - post-treatment	46.1 score on a scale Standard Deviation 62.9
Expression of Cell Cycle-related Proteins Ki67 pre-treatment - post-treatment	0.8 score on a scale Standard Deviation 16.8
Expression of Cell Cycle-related Proteins Caspase-3 active pre-treatment - post-treatment	0.7 score on a scale Standard Deviation 9

SECONDARY outcome

Timeframe: Baseline and Day 28 (+/- 5)

Population: The analysis was performed in the complete population of analysis (N = 36) and in the population of biomarkers (N = 31).

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.

Outcome measures

Outcome measures
Measure	Olaparib n=31 Participants Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Protein Expression of Biomarkers Related to PARP-inhibition P65 pre-treatment - post-treatment	-0.2 score on a scale Standard Deviation 0.9
Protein Expression of Biomarkers Related to PARP-inhibition PARP1 pre-treatment - post-treatment	10.3 score on a scale Standard Deviation 46.8
Protein Expression of Biomarkers Related to PARP-inhibition y-H2AX pre-treatment - post-treatment	-46.21 score on a scale Standard Deviation 67.7
Protein Expression of Biomarkers Related to PARP-inhibition VEGF pre-treatment - post-treatment	-9.4 score on a scale Standard Deviation 19.4
Protein Expression of Biomarkers Related to PARP-inhibition HIF-1α pre-treatment - post-treatment	76.9 score on a scale Standard Deviation 74.3
Protein Expression of Biomarkers Related to PARP-inhibition PTEN pre-treatment - post-treatment	3.2 score on a scale Standard Deviation 1
Protein Expression of Biomarkers Related to PARP-inhibition P50 pre-treatment - post-treatment	0.1 score on a scale Standard Deviation 0.8
Protein Expression of Biomarkers Related to PARP-inhibition P53 pre-treatment - post-treatment	0.1 score on a scale Standard Deviation 0.5
Protein Expression of Biomarkers Related to PARP-inhibition GLUT1 active pre-treatment - post-treatment	-20.8 score on a scale Standard Deviation 66.2
Protein Expression of Biomarkers Related to PARP-inhibition PHH3 pre-treatment - post-treatment	3.1 score on a scale Standard Deviation 5.2
Protein Expression of Biomarkers Related to PARP-inhibition ARID1A pre-treatment - post-treatment	20 score on a scale Standard Deviation 11

SECONDARY outcome

Timeframe: Days 7,14,21 and 28

Population: The analysis was performed in the overall population of analysis (N = 36)

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.

Outcome measures

Outcome measures
Measure	Olaparib n=36 Participants Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Plasma Levels of Olaparib Day 07	6.55 µg/mL Standard Deviation 2.75
Plasma Levels of Olaparib Day 14	5.61 µg/mL Standard Deviation 2.7
Plasma Levels of Olaparib Day 21	6.49 µg/mL Standard Deviation 2.95
Plasma Levels of Olaparib Day 28	4.7 µg/mL Standard Deviation 3.13

SECONDARY outcome

Timeframe: Up to 28 days (+/- 5)

Population: The analysis was performed in the complete population of analysis (N = 36) and took in account patients who discontinued study for drug-associated toxicity.

To assess the tolerability for all treated patients (N=36) according to NCI-CTCAE v.4.03.

Outcome measures

Outcome measures
Measure	Olaparib n=36 Participants Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Number of Participants With Olaparib-Associated Toxicities	3 Participants

Adverse Events

Olaparib

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Olaparib n=36 participants at risk Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Infections and infestations Post-surgical wound infection	2.8% 1/36 • Number of events 1 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.

Other adverse events

Other adverse events
Measure	Olaparib n=36 participants at risk Drug exposure has a limited duration 28 (+/- 5) days. Olaparib: Drug exposure has a limited duration 28 (+/- 5) days and at lower dose (600mg/day) than therapeutical accepted (800mg/day).
Gastrointestinal disorders Nausea	41.7% 15/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.
Blood and lymphatic system disorders Neutropenia	27.8% 10/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.
Blood and lymphatic system disorders Anemia	25.0% 9/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.
General disorders Asthenia	25.0% 9/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.
Gastrointestinal disorders Vomiting	16.7% 6/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.
Gastrointestinal disorders Diarrhea	13.9% 5/36 • Adverse events were collected from the first day of treatment initiation until to 28 days (+/- 7 days) after the last day of study treatment.

Additional Information

Director of Operations

Medica Scientia Innovation Research (MedSIR)

Phone: 0034 932 214 135

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place