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

University of Michigan Rogel Cancer Center

Status and phase

Completed

Phase 2

Phase 1

Conditions

Adenocarcinoma of the Pancreas

Treatments

Radiation: Radiation Therapy

Drug: Gemcitabine

Drug: MK-1775

Study type

Interventional

Funder types

Other

Identifiers

NCT02037230

HUM00079048 (Other Identifier)

UMCC 2013.094

Details and patient eligibility

About

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.

Enrollment

34 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.