Dose Escalation Trial of AZD1775 and Gemcitabine (+Radiation) for Unresectable Adenocarcinoma of the Pancreas
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|ClinicalTrials.gov Identifier: NCT02037230|
Recruitment Status : Active, not recruiting
First Posted : January 15, 2014
Last Update Posted : November 20, 2018
|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 :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 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|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2022|
|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 MK-1775 when used concurrently with gemcitabine and gemcitabine-radiation. [ Time Frame: 36 months post treatment ]At the end of the trial, once all evaluable subjects have completed observation, p(DLT|d) will be calculated for each dose using the tite-CRM method (one parameter logistic regression model with prior distribution on the parameter alpha).
- Percent Overall Survival (OS) [ Time Frame: 1 year post treatment ]Overall survival (OS) will be summarized by Kaplan-Meier curves and characterized by descriptive statistics such as median OS.
- Proportion of patients with phosphorylation inhibition of greater than 0 [ Time Frame: First Cycle of Treatment ]During the first cycle of treatment, patients will undergo 2 biopsies: 3 h after treatment with gemcitabine (but before MK-1775), and 2 hours after MK-1775. WEE1 signaling will be assessed using immunohistochemistry (IHC) to measure phosphorylation of various markers including Cdk1 (Y15). Inhibition will be quantified as the within subject change in the above markers between the two biopsy timepoints. Descriptive statistics of inhibition across subjects (for each marker) will be calculated and reported by dose level.
- Time from date of registration to date of documented disease progression [ Time Frame: 1 year post treatment ]
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|