Trial Outcomes & Findings for Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor AZD1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery (NCT NCT02194829)

NCT ID: NCT02194829

Last Updated: 2023-04-25

Results Overview

A dose-limiting toxicity (DLT) was defined by the occurrence of any of the toxicities listed in section 5.1.5 of the protocol that are possibly, probably, or definitely related to study drug(s) within the first cycle (4 weeks = 28 days).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Assessed at 28 days

Results posted on

2023-04-25

Participant Flow

A total of 8 patients were enrolled between August 19, 2014 and November 1, 2016.

Participant milestones

Participant milestones
Measure	Arm A (Phase I - Initial Dose Level) Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor AZD1775 PO daily on days 1, 2, 8, 9, 15, and 16.	Arm B ((Phase I - Dose Level -2) Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor AZD1775 as in Arm A.
Overall Study STARTED	2	6
Overall Study Received Protocol Therapy	2	5
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Phase I - Initial Dose Level) Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor AZD1775 PO daily on days 1, 2, 8, 9, 15, and 16.	Arm B ((Phase I - Dose Level -2) Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor AZD1775 as in Arm A.
Overall Study Adverse Event	2	2
Overall Study Death	0	1
Overall Study Disease progression	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Never started protocol therapy	0	1

Baseline Characteristics

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor AZD1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Phase I - Initial Dose Level) n=2 Participants Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor AZD1775 PO daily on days 1, 2, 8, 9, 15, and 16.	Arm B ((Phase I - Dose Level -2) n=5 Participants Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor AZD1775 as in Arm A.	Total n=7 Participants Total of all reporting groups
Age, Continuous	70.5 years n=5 Participants	73 years n=7 Participants	73 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at 28 days

Population: Only patients who received protocol therapy were included in this analysis.

Outcome measures

Outcome measures
Measure	Arm A (Phase I - Initial Dose Level) n=2 Participants Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor AZD1775 PO daily on days 1, 2, 8, 9, 15, and 16.	Arm B (Phase I - Dose Level -2) n=5 Participants Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor AZD1775 as in Arm A.
Number of Participants With Dose Limiting Toxicities (DLT)	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Assessed at Day 1 and Day 16

Population: Insufficient plasma samples were collected on this study so no pharmacokinetics analysis of AZD1775 in combination with nab-paclitaxel and gemcitabine was performed. Data were not collected. Consequently, no pharmacokinetics results of AZD1775 would be reported here.

Plasma was to be collected on Cycle 1 Day 1 and Cycle 1 Day 16 for the pharmacokinetics analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years

Population: This study stopped at phase I and did not move forward to the phase II part.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years

Population: This study stopped at phase I and did not move forward to the phase II part.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years

Population: This study stopped at phase I and did not move forward to the phase II part.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years

Population: This study stopped at phase I and did not move forward to the phase II part.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Phase I - Initial Dose Level)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Arm B (Phase I - Dose Level -2)

Serious events: 5 serious events

Other events: 5 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Phase I - Initial Dose Level) n=2 participants at risk Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor MK-1775 PO daily on days 1, 2, 8, 9, 15, and 16.	Arm B (Phase I - Dose Level -2) n=5 participants at risk Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor MK-1775 as in Arm A.
Investigations Alanine aminotransferase increased	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Alkaline phosphatase increased	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Aspartate aminotransferase increased	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Blood bilirubin increased	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Blood and lymphatic system disorders Anemia	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	40.0% 2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
General disorders Fever	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Gastrointestinal disorders Mucositis oral	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Infections and infestations Sepsis	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Infections and infestations Infections and infestations - Other, specify	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Lymphocyte count decreased	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	60.0% 3/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Neutrophil count decreased	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	40.0% 2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations Platelet count decreased	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	40.0% 2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Investigations White blood cell decreased	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	60.0% 3/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Metabolism and nutrition disorders Dehydration	100.0% 2/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	0.00% 0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Psychiatric disorders Irritability	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	20.0% 1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.
Vascular disorders Thromboembolic event	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.	40.0% 2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment All patients are included in the analyses of all-cause mortality and adverse events.