Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Gemcitabine

Pancrelipase

Pancreatin

Adavosertib

Antimetabolites

Enzyme Inhibitors

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 .

MK-1775

Gemcitabine 1000mg/m2 will be infused over 30 minutes on days 1 and 8 of a 3 -week treatment cycle.

52.5Gy in 25 fractions (2.1Gy/fraction), using intensity modulated radiation therapy (IMRT). Radiation therapy will be administered after chemotherapy.

Radiation Therapy

Theodore Lawrence, M.D., Ph.D.

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.

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

DOSE ESCALATION TRIAL OF THE Wee1 INHIBITOR AZD1775, IN COMBINATION WITH GEMCITABINE (+RADIATION) FOR PATIENTS WITH UNRESECTABLE ADENOCARCINOMA OF THE PANCREAS

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).

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 (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 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.

University of Michigan Rogel Cancer Center

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 100 mg

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 125 mg

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 150 mg

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

AZD-1775 175 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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.

AZD1775 (MK-1775), Gemcitabine, Radiation Therapy

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

Maximum Tolerated Dose (MTD) of AZD1775 (MK-1775) When Used Concurrently With Gemcitabine and Radiation Therapy.

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

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial