NCT01420081

A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer

Terminated Phase 2 Results posted Last updated 8 January 2019

What this trial tests

Phase 2 trial testing PF-05212384 in Endometrial Neoplasms in 67 participants. Terminated before completion.

Timeline

19 January 2012

Primary endpoint
30 April 2014

25 December 2015

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	67
Start date	19 January 2012
Primary completion	30 April 2014
Estimated completion	25 December 2015
Sites	51 locations across Japan, Russia, United Kingdom, Poland, Canada, Australia, United States, Spain

Drugs / interventions tested

• PF-05212384 — full drug profile →
• PF-05212384 — full drug profile →
• PF-05212384 — full drug profile →

Conditions studied

• Endometrial Neoplasms — all drugs for Endometrial Neoplasms →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, female only, with Endometrial Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Benefit Response for PF-04691502 Primary · 16 weeks from Cycle 1 Day 1

Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The outcome data table below presents the number of participants with clinical benefit response as "yes" or "no". On 09 Oct 2012, Pfizer decided to stop enrollment into PF-04691502. While tumor assessment for PF-04691502 was included as a listing in the final report, formal efficacy analysis for PF-04691502 was not performed.

Participants with "Yes" response

Group	Value	95% CI
PF-04691502 (PI3K Basal)	1
PF-04691502 (PI3K Activated)	0

Participants with "No" response

Group	Value	95% CI
PF-04691502 (PI3K Basal)	3
PF-04691502 (PI3K Activated)	11

Percentage of Participants With Clinical Benefit Response for PF-05212384 Primary · 16 weeks from Cycle 1 Day 1

Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The primary analysis is based on the clinical benefit rate which is calculated as proportion of participants with a clinical benefit response relative to total number of response evaluable participants. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as \>=30% decrease in the sum of the longest diameter of target lesions; S

Group	Value	95% CI
PF-05212384 (PI3K Basal)	52.6	28.9 – 75.6
PF-05212384 (PI3K Activated)	26.3	9.1 – 51.2
PF-05212384 (PI3K Basal + Activated)	39.5	24.0 – 56.6

Objective Response for PF-04691502 Secondary · Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)

Objective response is defined as CR or PR. CR: Complete response: 2 or more objective statuses of CR a minimum of 4 weeks apart documented before PD. Partial response: 2 or more objective statuses of PR or better a minimum of 4 weeks apart documented before PD, but not qualifying as CR. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as \>=30% decrease in the sum of the longest diameter of target lesions. The outcome data table below presents the number of participants with objective response as "yes" or "no". On 09 Oct 2012, Pfizer decided to

Participants with "Yes" response

Group	Value	95% CI
PF-04691502 (PI3K Basal)	0
PF-04691502 (PI3K Activated)	0

Participants with "No" response

Group	Value	95% CI
PF-04691502 (PI3K Basal)	4
PF-04691502 (PI3K Activated)	11

Percentage of Participants With Objective Response for PF-05212384 Secondary · Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)

Objective response is defined as CR or PR. CR: Complete response: 2 or more objective statuses of CR a minimum of 4 weeks apart documented before PD. Partial response: 2 or more objective statuses of PR or better a minimum of 4 weeks apart documented before PD, but not qualifying as CR. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as \>=30% decrease in the sum of the longest diameter of target lesions.

Group	Value	95% CI
PF-05212384 (PI3K Basal)	21.1	6.1 – 45.6
PF-05212384 (PI3K Activated)	15.8	3.4 – 39.6
PF-05212384 (PI3K Basal + Activated)	18.4	7.7 – 34.3

Progression Free Survival for PF-04691502 Secondary · From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)

PFS is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the median. Approximate 95% confidence interval corresponding to this estimate was computed. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions. On 09 Oct 2012, Pfizer decided to stop enrollment into PF-0469

Participant 1

Group	Value	95% CI
PF-04691502 (PI3K Basal)	1
PF-04691502 (PI3K Activated)	0

Participant 2

Group	Value	95% CI
PF-04691502 (PI3K Basal)	108
PF-04691502 (PI3K Activated)	0

Participant 3

Group	Value	95% CI
PF-04691502 (PI3K Basal)	50
PF-04691502 (PI3K Activated)	0

Participant 4

Group	Value	95% CI
PF-04691502 (PI3K Basal)	199
PF-04691502 (PI3K Activated)	0

Participant 5

Group	Value	95% CI
PF-04691502 (PI3K Basal)	0
PF-04691502 (PI3K Activated)	54

Participant 6

Group	Value	95% CI
PF-04691502 (PI3K Basal)	0
PF-04691502 (PI3K Activated)	55

Participant 7

Group	Value	95% CI
PF-04691502 (PI3K Basal)	0
PF-04691502 (PI3K Activated)	51

Participant 8

Group	Value	95% CI
PF-04691502 (PI3K Basal)	0
PF-04691502 (PI3K Activated)	1

Progression Free Survival for PF-05212384 Secondary · From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)

PFS is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the median. Approximate 95% confidence interval corresponding to this estimate was computed. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.

Group	Value	95% CI
PF-05212384 (PI3K Basal)	112.0	59.0 – 167.0
PF-05212384 (PI3K Activated)	89.0	56.0 – 172.0
PF-05212384 (PI3K Basal + Activated)	108.0	62.0 – 149.0

Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384 Secondary · 6 months

Progression free survival is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the probability of remaining progression-free at 6 months (based on Kaplan-Meier estimates). Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.

Group	Value	95% CI
PF-05212384 (PI3K Basal)	23.2	7.3 – 44.1
PF-05212384 (PI3K Activated)	25.0	7.8 – 47.2
PF-05212384 (PI3K Basal + Activated)	24.3	11.6 – 39.5

Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glucose (mg/dL) Secondary · Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days

PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

Baseline

Group	Value	95% CI
PF-05212384 (PI3K Basal)	98.5	± 12.76
PF-05212384 (PI3K Activated)	101.7	± 26.56
PF-05212384 (PI3K Basal + Activated)	100.1	± 20.60

Cycle 1 Day 15 (n=18,17,35)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	105.3	± 18.44
PF-05212384 (PI3K Activated)	117.2	± 61.04
PF-05212384 (PI3K Basal + Activated)	111.1	± 44.26

Cycle 1 Day 22 (n=2,1,3)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	103.0	± 16.34
PF-05212384 (PI3K Activated)	120.1	± 0
PF-05212384 (PI3K Basal + Activated)	108.7	± 15.19

Cycle 2 Day 1 (n=17,14,31)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	103.7	± 19.31
PF-05212384 (PI3K Activated)	114.0	± 39.42
PF-05212384 (PI3K Basal + Activated)	108.3	± 29.99

Cycle 2 Day 15 (n=17,8,25)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	104.8	± 13.94
PF-05212384 (PI3K Activated)	106.4	± 19.36
PF-05212384 (PI3K Basal + Activated)	105.3	± 15.47

Cycle 3 Day 1 (n=14,10,24)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	100.6	± 16.29
PF-05212384 (PI3K Activated)	125.9	± 74.50
PF-05212384 (PI3K Basal + Activated)	111.1	± 49.85

Cycle 4 Day 1 (n=12,7,19)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	96.3	± 10.40
PF-05212384 (PI3K Activated)	98.9	± 10.20
PF-05212384 (PI3K Basal + Activated)	97.3	± 10.12

Cycle 5 Day 1 (n=9,4,13)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	103.2	± 15.17
PF-05212384 (PI3K Activated)	112.2	± 24.37
PF-05212384 (PI3K Basal + Activated)	106.0	± 17.90

Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL) Secondary · Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days

PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

Baseline

Group	Value	95% CI
PF-05212384 (PI3K Basal)	15.2	± 12.68
PF-05212384 (PI3K Activated)	14.4	± 7.03
PF-05212384 (PI3K Basal + Activated)	14.8	± 10.36

Cycle 1 Day 15 (n=16,12,28)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	23.6	± 14.69
PF-05212384 (PI3K Activated)	35.9	± 37.05
PF-05212384 (PI3K Basal + Activated)	28.9	± 26.79

Cycle 1 Day 22 (n=2,1,3)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	57.6	± 51.18
PF-05212384 (PI3K Activated)	29.1	± 0
PF-05212384 (PI3K Basal + Activated)	48.1	± 39.75

Cycle 2 Day 1 (n=17,10,27)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	30.3	± 28.92
PF-05212384 (PI3K Activated)	28.9	± 27.85
PF-05212384 (PI3K Basal + Activated)	29.8	± 27.99

Cycle 2 Day 15 (n=14,6,20)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	28.2	± 29.56
PF-05212384 (PI3K Activated)	21.9	± 10.49
PF-05212384 (PI3K Basal + Activated)	26.3	± 25.21

Cycle 3 Day 1 (n=13,9,22)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	20.7	± 13.65
PF-05212384 (PI3K Activated)	35.1	± 38.66
PF-05212384 (PI3K Basal + Activated)	26.6	± 26.99

Cycle 4 Day 1 (n=11,6,17)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	17.1	± 10.04
PF-05212384 (PI3K Activated)	24.8	± 32.32
PF-05212384 (PI3K Basal + Activated)	19.8	± 20.10

Cycle 5 Day 1 (n=7,4,11)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	17.0	± 15.56
PF-05212384 (PI3K Activated)	15.7	± 6.20
PF-05212384 (PI3K Basal + Activated)	16.5	± 12.54

Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c) Secondary · Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days

PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

Baseline (n=15,14,29)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	7.8	± 8.58
PF-05212384 (PI3K Activated)	7.5	± 6.15
PF-05212384 (PI3K Basal + Activated)	7.7	± 7.37

Cycle 1 Day 15 (n=4,2,6)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	14.7	± 19.00
PF-05212384 (PI3K Activated)	7.1	± 1.34
PF-05212384 (PI3K Basal + Activated)	12.2	± 15.25

Cycle 2 Day 1 (n=15,13,28)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	8.4	± 9.66
PF-05212384 (PI3K Activated)	6.7	± 1.16
PF-05212384 (PI3K Basal + Activated)	7.6	± 7.05

Cycle 2 Day 15 (n=3,0,3)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	6.7	± 0.71
PF-05212384 (PI3K Activated)	NA	± NA
PF-05212384 (PI3K Basal + Activated)	6.7	± 0.71

Cycle 3 Day 1 (n=10,4,14)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	6.0	± 0.78
PF-05212384 (PI3K Activated)	7.3	± 1.70
PF-05212384 (PI3K Basal + Activated)	6.4	± 1.19

Cycle 4 Day 1 (n=12,7,19)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	8.9	± 10.13
PF-05212384 (PI3K Activated)	6.9	± 1.05
PF-05212384 (PI3K Basal + Activated)	8.2	± 8.01

Cycle 5 Day 1 (n=8,2,10)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	5.9	± 0.89
PF-05212384 (PI3K Activated)	31.5	± 36.06
PF-05212384 (PI3K Basal + Activated)	11.0	± 16.17

Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL) Secondary · Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days

PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

Baseline (n=11,4,15)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	213	± 54.48
PF-05212384 (PI3K Activated)	186.5	± 52.43
PF-05212384 (PI3K Basal + Activated)	205.9	± 53.45

Cycle 1 Day 28 (n=15,7,22)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	214.9	± 49.15
PF-05212384 (PI3K Activated)	161.6	± 86.51
PF-05212384 (PI3K Basal + Activated)	198.0	± 66.28

Cycle 2 Day 28 (n=16,6,22)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	229.8	± 44.31
PF-05212384 (PI3K Activated)	127.9	± 108.69
PF-05212384 (PI3K Basal + Activated)	202.0	± 79.83

Cycle 3 Day 28 (n=11,4,15)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	230.5	± 48.63
PF-05212384 (PI3K Activated)	137.6	± 107.02
PF-05212384 (PI3K Basal + Activated)	205.7	± 77.15

Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL) Secondary · Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days

PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

Baseline (n=11,4,15)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	104.2	± 40.95
PF-05212384 (PI3K Activated)	133.4	± 25.75
PF-05212384 (PI3K Basal + Activated)	112.0	± 38.96

Cycle 1 Day 28 (n=15,7,22)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	136.9	± 70.03
PF-05212384 (PI3K Activated)	134.5	± 57.21
PF-05212384 (PI3K Basal + Activated)	136.1	± 64.85

Cycle 2 Day 28 (n=16,6,22)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	133.2	± 71.40
PF-05212384 (PI3K Activated)	117.1	± 62.77
PF-05212384 (PI3K Basal + Activated)	128.8	± 68.07

Cycle 3 Day 28 (n=10,4,14)

Group	Value	95% CI
PF-05212384 (PI3K Basal)	119.9	± 64.22
PF-05212384 (PI3K Activated)	130.4	± 58.01
PF-05212384 (PI3K Basal + Activated)	122.9	± 60.47

Adverse events — posted to ClinicalTrials.gov

Time frame: Maximum of treatment duration (i.e., 21 to 169 days for the PF 04691502 [PI3K basal and activated], 29 to 345 days for PF 05212384 PI3K basal and 1 to 400 days for PF 05212384 PI3K activated) + 28 days across all participants.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-04691502 8 mg (PI3K Basal)

Serious: 3/5 (60%)

Deaths: —

PF-04691502 6 mg (PI3K Basal)

Serious: 1/1 (100%)

Deaths: —

PF-04691502 8 mg (PI3K Activated)

Serious: 7/9 (78%)

Deaths: —

PF-04691502 6 mg (PI3K Activated)

Serious: 1/3 (33%)

Deaths: —

PF-05212384 154 mg (PI3K Basal)

Serious: 3/21 (14%)

Deaths: —

PF-05212384 154 mg (PI3K Activated)

Serious: 10/19 (53%)

Deaths: —

Lead-in-cohort (LIC) PF-04691502 (4 mg)

Serious: 1/3 (33%)

Deaths: —

LIC PF-05212384 (89 mg)

Serious: 0/3 (0%)

Deaths: —

LIC PF-05212384 (154 mg)

Serious: 1/3 (33%)

Deaths: —

Serious adverse events (32 terms)

Reaction	System	PF-04691502 8 mg (PI3K Bas…	PF-04691502 6 mg (PI3K Bas…	PF-04691502 8 mg (PI3K Act…	PF-04691502 6 mg (PI3K Act…	PF-05212384 154 mg (PI3K B…	PF-05212384 154 mg (PI3K A…	Lead-in-cohort (LIC) PF-04…	LIC PF-05212384 (89 mg)	LIC PF-05212384 (154 mg)
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Disease Progression	General disorders	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Cardiac Failure	Cardiac disorders	—	—	—	—	—	—	—	—	—
Large Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Oral Pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—
Lung Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumocystis Jirovecii Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—
Pyelonephritis	Infections and infestations	—	—	—	—	—	—	—	—	—
Skin Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Lymphocyte Count Decreased	Investigations	—	—	—	—	—	—	—	—	—
Diabetic Ketoacidosis	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Fistula	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Gastric Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—
Cerebrovascular Accident	Nervous system disorders	—	—	—	—	—	—	—	—	—
Acute Kidney Injury	Renal and urinary disorders	—	—	—	—	—	—	—	—	—

Other adverse events (223 terms — click to expand)

Reaction	System	PF-04691502 8 mg (PI3K Bas…	PF-04691502 6 mg (PI3K Bas…	PF-04691502 8 mg (PI3K Act…	PF-04691502 6 mg (PI3K Act…	PF-05212384 154 mg (PI3K B…	PF-05212384 154 mg (PI3K A…	Lead-in-cohort (LIC) PF-04…	LIC PF-05212384 (89 mg)	LIC PF-05212384 (154 mg)
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Mucosal Inflammation	General disorders	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Oedema Peripheral	General disorders	—	—	—	—	—	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Dry Mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—	—	—
Oral Herpes	Infections and infestations	—	—	—	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Weight Decreased	Investigations	—	—	—	—	—	—	—	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—	—	—	—	—
Vaginal Haemorrhage	Reproductive system and breast disorders	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Diarrhoea, Disease Progression, Pneumonia, Urinary Tract Infection, Pneumonitis, Pulmonary Embolism, Cardiac Failure, Large Intestinal Obstruction.

Data from ClinicalTrials.gov NCT01420081 adverse events section.

Sponsor's own description

This study will investigate the individual safety and efficacy of two dual PI3K/mTOR inhibitors in patients with recurrent endometrial cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting mTOR for cancer therapy.
   Hua H, Kong Q, Zhang H, Wang J, et al · · 2019 · cited 678× · PMID 31277692 · DOI 10.1186/s13045-019-0754-1
2. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.
   Panwar V, Singh A, Bhatt M, Tonk RK, et al · · 2023 · cited 628× · PMID 37779156 · DOI 10.1038/s41392-023-01608-z
3. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
   Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
4. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance.
   McCubrey JA, Steelman LS, Chappell WH, Abrams SL, et al · · 2012 · cited 242× · PMID 23085539 · DOI 10.18632/oncotarget.659
5. Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.
   Wang Q, Peng H, Qi X, Wu M, et al · · 2020 · cited 114× · PMID 32728057 · DOI 10.1038/s41392-020-0199-6
6. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer.
   Shapiro GI, Bell-McGuinn KM, Molina JR, Bendell J, et al · · 2015 · cited 99× · PMID 25652454 · DOI 10.1158/1078-0432.ccr-14-1306
7. Targeting the RAS oncogene.
   Takashima A, Faller DV. · · 2013 · cited 95× · PMID 23360111 · DOI 10.1517/14728222.2013.764990
8. The genomics and genetics of endometrial cancer.
   O'Hara AJ, Bell DW. · · 2012 · cited 86× · PMID 22888282 · DOI 10.2147/agg.s28953