Dose Escalation Trial of AZD1775 and Gemcitabine (+Radiation) for Unresectable Adenocarcinoma of the Pancreas

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02037230
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The investigators' long-term goal is to improve the survival of patients with pancreatic cancer by enhancing the efficacy of gemcitabine-radiation by adding the Wee1 inhibitor MK-1775.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas	Drug: MK-1775; Drug: Gemcitabine; Radiation: Radiation Therapy	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: DOSE ESCALATION TRIAL OF THE Wee1 INHIBITOR AZD1775, IN COMBINATION WITH GEMCITABINE (+RADIATION) FOR PATIENTS WITH UNRESECTABLE ADENOCARCINOMA OF THE PANCREAS
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: MK-1775/ Gemcitabine/ Radiation Therapy

Drug: MK-1775; MK-1775 will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle .; Drug: Gemcitabine; Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle.; Radiation: Radiation Therapy; 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy.

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy. [The observation period for MTD is defined as the first 4 cycles of treatment (with a 3 week break between cycle 3 and cycle 4), for a total of 105 days in length.]

   Probability of dose limiting toxicities was calculated for each dose (p[DLT/d]) using the Time to Event Continual Reassessment Method (TITE-CRM). The target DLT rate was 0.30. Dose level 1 (150 mg AZD1775) was determined to be the MTD and recommended phase 2 dose (RP2D).

Secondary Outcome Measures

1. Number of Patients With Phosphorylation Inhibition of Greater Than 0 [First cycle of treatment]

   During the first cycle of treatment, patients underwent 2 biopsies: 3 h after treatment with gemcitabine (but before MK- 1775), and 2 hours after MK-1775. WEE1 signaling was assessed using immunohistochemistry (IHC) to measure phosphorylation of various markers including Cdk1 (Y15). Inhibition was quantified as the within subject change in the above markers between the two biopsy timepoints. Descriptive statistics of inhibition across subjects (for each marker) were calculated and reported by dose level.

2. Overall Survival [Up to 48 months following treatment]

   Overall survival (OS) summarized by Kaplan-Meier curves and characterized by descriptive statistics such as median OS. The time frame for data collection for OS varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.

3. Time From Date of Registration to Date of Documented Disease Progression [Up to 48 months following treatment]

   Time from date of registration to date of documented disease progression summarized by Kaplan-Meier method. The time frame for data collection varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have pathologically confirmed adenocarcinoma of the pancreas.

• Patients will have unresectable disease, defined radiographically as >180 degrees involvement of the superior mesenteric artery or celiac trunk or SMV/portal vein impingement that cannot be surgically reconstructed, in the absence of distant metastasis..

• Patients must have a Zubrod performance status (measure of general well being that ranges from 0 to 5 where 0 represents perfect health) of < 2.

• Patients must have adequate organ function defined as follows: absolute neutrophil count of ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum creatinine ≤ 2 mg/dl, total bilirubin ≤ 3, (with relief of biliary obstruction if present (PTC tube or endobiliary stent)) and AST < 5 times the upper limit of normal.

• Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months after the trial. Patients must not be breastfeeding.

• Patients must be aware of the investigational nature of the therapy and provide written informed consent.

• Patients must be at least 18 years old.

Exclusion Criteria:

• Other serious uncontrolled concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.

• A history of previous chemotherapy for pancreatic cancer or abdominal radiation therapy.

• The use of any investigational agent in the month before enrollment into the study.

• Inability to discontinue a prescription or non-prescription drugs or other products known to be metabolized by CYP3A4, or to inhibit or induce CYP3A4 prior to Day 1 of dosing and to withhold throughout the study until 2 weeks after the last dose of study medication. Medications of particular concern are the following inhibitors of CYP3A4: azole antifungals (ketoconazole itraconazole, fluconazole and voriconazole), macrolide antibiotics (erythromycin, clarithromycin), cimetidine, aprepitant, HIV protease inhibitors, nefazodone and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin. Substrates of CYP3A4 include statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Theodore Lawrence, M.D., Ph.D., University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 7, 2017

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02037230
• Other Study ID Numbers: UMCC 2013.094; HUM00079048; NCT01916551
• First Posted: Jan 15, 2014
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Adavosertib

Study Results

Participant Flow

Arm/Group Title	AZD-1775 100 mg	AZD-1775 125 mg	AZD-1775 150 mg	AZD-1775 175 mg
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3
Period Title: Overall Study
STARTED	1	13	9	11
Completed 4 Cycles of Treatment	1	9	7	9
COMPLETED	0	7	3	5
NOT COMPLETED	1	6	6	6

Baseline Characteristics

Arm/Group Title	AZD-1775 100 mg	AZD-1775 125 mg	AZD-1775 150 mg	AZD-1775 175 mg	Total
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	Total of all reporting groups
Overall Participants	1	13	9	11	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	74	66	62	60	68
Sex: Female, Male (Count of Participants)
Female	1 100%	6 46.2%	4 44.4%	4 36.4%	15 44.1%
Male	0 0%	7 53.8%	5 55.6%	7 63.6%	19 55.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	1 9.1%	1 2.9%
Not Hispanic or Latino	1 100%	11 84.6%	9 100%	10 90.9%	31 91.2%
Unknown or Not Reported	0 0%	2 15.4%	0 0%	0 0%	2 5.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	2 22.2%	0 0%	2 5.9%
White	1 100%	13 100%	7 77.8%	11 100%	32 94.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy.
Description	Probability of dose limiting toxicities was calculated for each dose (p[DLT/d]) using the Time to Event Continual Reassessment Method (TITE-CRM). The target DLT rate was 0.30. Dose level 1 (150 mg AZD1775) was determined to be the MTD and recommended phase 2 dose (RP2D).
Time Frame	The observation period for MTD is defined as the first 4 cycles of treatment (with a 3 week break between cycle 3 and cycle 4), for a total of 105 days in length.

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug were evaluable for MTD.

Arm/Group Title	AZD1775 (MK-1775), Gemcitabine, Radiation Therapy
Arm/Group Description	AZD1775 (MK-1775) will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy.
Measure Participants	34
Number [mg]	150

2. Secondary Outcome

Title	Number of Patients With Phosphorylation Inhibition of Greater Than 0
Description	During the first cycle of treatment, patients underwent 2 biopsies: 3 h after treatment with gemcitabine (but before MK- 1775), and 2 hours after MK-1775. WEE1 signaling was assessed using immunohistochemistry (IHC) to measure phosphorylation of various markers including Cdk1 (Y15). Inhibition was quantified as the within subject change in the above markers between the two biopsy timepoints. Descriptive statistics of inhibition across subjects (for each marker) were calculated and reported by dose level.
Time Frame	First cycle of treatment

Outcome Measure Data

Analysis Population Description

20 participants were evaluable for this outcome measure. Two sequential skin punch biopsies were obtained from 20 of the 34 study participants.

Arm/Group Title	AZD-1775 100 mg	AZD-1775 125 mg	AZD-1775 150 mg	AZD-1775 175 mg
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3
Measure Participants	1	8	5	6
Number [participants]	1 100%	7 53.8%	3 33.3%	5 45.5%

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) summarized by Kaplan-Meier curves and characterized by descriptive statistics such as median OS. The time frame for data collection for OS varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.
Time Frame	Up to 48 months following treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD-1775 100 mg	AZD-1775 125 mg	AZD-1775 150 mg	AZD-1775 175 mg
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3
Measure Participants	1	13	9	11
Median (90% Confidence Interval) [months]	21.96	21.73	23.84	22.45

4. Secondary Outcome

Title	Time From Date of Registration to Date of Documented Disease Progression
Description	Time from date of registration to date of documented disease progression summarized by Kaplan-Meier method. The time frame for data collection varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.
Time Frame	Up to 48 months following treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD-1775 100 mg	AZD-1775 125 mg	AZD-1775 150 mg	AZD-1775 175 mg
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3	AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3
Measure Participants	1	13	9	11
Median (90% Confidence Interval) [months]	8.05	9.44	9.90	6.08

Adverse Events

Time Frame	Adverse events were collected during the course of treatment (26 weeks). The time frame for data collection for all-cause mortality varied depending on the length of patient follow-up, which ranged from 1.8 months to 47.2 months. All-cause mortality includes all observed deaths while the study was ongoing, regardless of duration of patient follow-up. Patients who enrolled soon after the study opened may have been followed longer than patients who enrolled later, toward the end of the study.
Arm/Group Title	AZD-1775 100 mg		AZD-1775 125 mg		AZD-1775 150 mg		AZD-1775 175 mg
Arm/Group Description	AZD-1775 (MK-1775) 100 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3		AZD-1775 (MK-1775) 125 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3		AZD-1775 (MK-1775) 150 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3		AZD-1775 (MK-1775) 175 mg will be given as an oral capsule on days 1 and 2, and on days 8 and 9 of every 3-week cycle . Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle. Radiation Therapy: 52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy. only in cycles 2 and 3
All Cause Mortality
	AZD-1775 100 mg		AZD-1775 125 mg		AZD-1775 150 mg		AZD-1775 175 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		9/13 (69.2%)		5/9 (55.6%)		6/11 (54.5%)
Serious Adverse Events
	AZD-1775 100 mg		AZD-1775 125 mg		AZD-1775 150 mg		AZD-1775 175 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		5/13 (38.5%)		4/9 (44.4%)		8/11 (72.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	3/11 (27.3%)	3
Septic shock	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	1/11 (9.1%)	1
Cardiac disorders
Myocardial infarction	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	0/11 (0%)	0
Gastrointestinal disorders
Abdominal Pain	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	0/11 (0%)	0
ALT/AST elevation	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	0/11 (0%)	0
Anorexia, nausea/vomiting	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	2/11 (18.2%)	2
Cholangitis	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	1/11 (9.1%)	1
Colitis	0/1 (0%)	0	2/13 (15.4%)	2	0/9 (0%)	0	0/11 (0%)	0
Diverticulitis	0/1 (0%)	0	0/13 (0%)	0	0/9 (0%)	0	1/11 (9.1%)	1
GI bleed	1/1 (100%)	1	0/13 (0%)	0	0/9 (0%)	0	0/11 (0%)	0
General disorders
Fatigue	0/1 (0%)	0	0/13 (0%)	0	0/9 (0%)	0	3/11 (27.3%)	3
Fever	0/1 (0%)	0	0/13 (0%)	0	2/9 (22.2%)	2	1/11 (9.1%)	1
Altered mental status	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Pulmonary embolus	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	AZD-1775 100 mg		AZD-1775 125 mg		AZD-1775 150 mg		AZD-1775 175 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		3/13 (23.1%)		3/9 (33.3%)		4/11 (36.4%)
Gastrointestinal disorders
Abdominal Pain	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
General disorders
Fever	0/1 (0%)	0	0/13 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Fatigue	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	1/11 (9.1%)	1
Edema	0/1 (0%)	0	0/13 (0%)	0	0/9 (0%)	0	1/11 (9.1%)	1
Metabolism and nutrition disorders
Anorexia	0/1 (0%)	0	1/13 (7.7%)	1	1/9 (11.1%)	1	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Pruritic Rash	0/1 (0%)	0	1/13 (7.7%)	1	0/9 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.