Dose Escalation Trial of AZD1775 and Gemcitabine (+Radiation) for Unresectable Adenocarcinoma of the Pancreas
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|ClinicalTrials.gov Identifier: NCT02037230|
Recruitment Status : Completed
First Posted : January 15, 2014
Results First Posted : February 17, 2020
Last Update Posted : February 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Pancreas||Drug: MK-1775 Drug: Gemcitabine Radiation: Radiation Therapy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||January 2014|
|Actual Primary Completion Date :||August 2018|
|Actual Study Completion Date :||August 2018|
|Experimental: MK-1775/ Gemcitabine/ Radiation Therapy||
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: Radiation Therapy
52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy.
- Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy. [ 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. ]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).
- Number of Patients With Phosphorylation Inhibition of Greater Than 0 [ Time Frame: 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.
- Overall Survival [ Time Frame: 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.
- Time From Date of Registration to Date of Documented Disease Progression [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02037230
|United States, Michigan|
|University of Michigan Hospital|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Theodore Lawrence, M.D., Ph.D.||University of Michigan Rogel Cancer Center|