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

NCT02037230 | Completed Phase 1 Results DMC

• 2 other identifiers: UMCC 2013.094HUM00079048
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma of the Pancreas

Outcome Measures

Primary Outcomes (1)

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

  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).

  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 (3)

• Number of Patients With Phosphorylation Inhibition of Greater Than 0

  First cycle of treatment

• Overall Survival

  Up to 48 months following treatment

• Time From Date of Registration to Date of Documented Disease Progression

  Up to 48 months following treatment

Study Arms (1)

MK-1775/ Gemcitabine/ Radiation Therapy

EXPERIMENTAL

Drug: MK-1775; Drug: Gemcitabine; Radiation: Radiation Therapy

Interventions

MK-1775 DRUG

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/ Radiation Therapy

Gemcitabine DRUG

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

MK-1775/ Gemcitabine/ Radiation Therapy

Radiation Therapy RADIATION

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

MK-1775/ Gemcitabine/ Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 31398082 DERIVED

MeSH Terms

Interventions

adavosertib; Gemcitabine; Radiotherapy

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics

Results Point of Contact

• Title: Theodore Lawrence, M.D., Ph.D.
• Organization: University of Michigan Rogel Cancer Center

tsl@umich.edu

734-647-9955

Study Officials

• Theodore Lawrence, M.D., Ph.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 15, 2014
• Study Start: January 1, 2014
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: February 17, 2020
• Results First Posted: February 17, 2020

Record last verified: 2020-02

Locations

US (1)