Clinical trial NCT02037230: Dose Escalation Trial of AZD1775 and Gemcitabine (+Radiation) for Unresectable Adenocarcinoma of the Pancreas
Official title: DOSE ESCALATION TRIAL OF THE Wee1 INHIBITOR AZD1775, IN COMBINATION WITH GEMCITABINE (+RADIATION) FOR PATIENTS WITH UNRESECTABLE ADENOCARCINOMA OF THE PANCREAS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma of the Pancreas
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2014-01-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy.
timeFrame: 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.
Secondary outcomes:
measure: Number of Patients With Phosphorylation Inhibition of Greater Than 0
timeFrame: First cycle of treatment
measure: Overall Survival
timeFrame: Up to 48 months following treatment
measure: Time From Date of Registration to Date of Documented Disease Progression
timeFrame: Up to 48 months following treatment
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Theodore Lawrence, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cuneo KC, Morgan MA, Sahai V, Schipper MJ, Parsels LA, Parsels JD, Devasia T, Al-Hawaray M, Cho CS, Nathan H, Maybaum J, Zalupski MM, Lawrence TS. Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer. J Clin Oncol. 2019 Oct 10;37(29):2643-2650. doi: 10.1200/JCO.19.00730. Epub 2019 Aug 9.