Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor AZD1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery

NCT02194829 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2014-01425EA2131U10CA180820U10CA021115
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of WEE1 inhibitor AZD1775 when given together with paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride and how well they work in treating patients with previously untreated pancreatic cancer that has spread to another place in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. WEE1 inhibitor AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride are more effective with or without WEE1 inhibitor AZD1775 in treating patients with pancreatic cancer.

Conditions

Metastatic Pancreatic Adenocarcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Unresectable Pancreatic Carcinoma

Keywords

Metastatic Pancreatic Adenocarcinoma; Nab-paclitaxel; Gemcitabine; AZD1775

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLT)

  A dose-limiting toxicity (DLT) was defined by the occurrence of any of the toxicities listed in section 5.1.5 of the protocol that are possibly, probably, or definitely related to study drug(s) within the first cycle (4 weeks = 28 days).

  Assessed at 28 days

• To Determine the Pharmacokinetics of AZD1775 in Combination With Nab-paclitaxel and Gemcitabine

  Plasma was to be collected on Cycle 1 Day 1 and Cycle 1 Day 16 for the pharmacokinetics analysis.

  Assessed at Day 1 and Day 16

• Progression-free Survival

  Assessed every 3 months for 2 years

Secondary Outcomes (3)

• Overall Survival

  Assessed every 3 months for 2 years

• Response Rate

  Assessed every 3 months for 2 years

• Disease Control Rate

  Assessed every 3 months for 2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive WEE1 inhibitor AZD1775 PO daily on days 1, 2, 8, 9, 15, and 16.

Drug: AZD1775; Drug: Gemcitabine; Drug: Nab-paclitaxel

Arm B

EXPERIMENTAL

Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor AZD1775 as in Arm A.

Drug: AZD1775; Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

AZD1775 DRUG

Given PO

Also known as: Adavosertib, MK-1775

Arm A; Arm B

Gemcitabine DRUG

Given IV

Also known as: 2'-Deoxy-2', 2'-difluorocytidine monohydrochloride, Gemzar

Arm A; Arm B

Nab-paclitaxel DRUG

Given IV

Also known as: ABI-007, paclitaxel protein-bound particles for injectable suspension

Arm A; Arm B

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 histologically or cytologically confirmed metastatic or unresectable locally advanced adenocarcinoma of the pancreas. Prior therapy with a non-gemcitabine based regimen is permitted.
• Previous neo-adjuvant or adjuvant treatment is allowed provided that it was given \>= 6 months prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have a life expectancy of \>= 12 weeks
• Patients may have had prior radiotherapy for metastatic disease as long as it was \> 4 weeks prior to registration and the patient has recovered from adverse events associated with the radiotherapy
• Patients must be able to swallow capsules whole
• Patients must be able to tolerate computed tomography (CT), magnetic resonance imaging (MRI) or PET imaging including contrast agents
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal and barrier method of birth control; two barrier methods of birth control; abstinence) for the duration of study treatment and for 3 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; should a man impregnate or suspect that he has impregnated a woman while participating in this study, he should inform his treating physician immediately
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 X institutional upper limit of normal (ULN) or =\< 5 X ULN if the patient has liver metastases
• Creatinine =\< 1.5 mg/dL or creatinine clearance (Cockcroft-Gault) \>= 60 mL/min for patients with creatinine levels above institutional upper limit of normal (ULN)

You may not qualify if:

• Receiving any other investigational agents concurrently
• Have received any other investigational agents =\< 4 weeks prior to registration
• Pre-existing \> grade 1 motor or sensory neuropathy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, gemcitabine or AZD1775
• Major surgical procedures \<=28 days of beginning study treatment or minor surgical procedures \<=7 days
• Taking current medications or substances that are inhibitors of CYP3A4, inhibitors or substrates of P-glycoprotein or inhibitors of breast cancer resistance protein (BCRP)
• Uncontrolled serious medical illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
• Patients with known human immunodeficiency virus (HIV) and cluster of differentiation (CD)4 count is =\< 200 cell/mm\^3 or receiving antiretroviral therapy due to potential unfavorable interaction of the agents with the study treatment
• Previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
• Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ)
• Prior malignancy completely excised or removed and patient has been continuously disease free for \> 5 years
• Pregnant or breast-feeding
• Females of childbearing potential must have a blood test or urine study within 5 days prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• At least18 years of age
• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

adavosertib; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Biostatistics Center

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Jennifer R Eads

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 18, 2014
• Study Start: August 19, 2014
• Primary Completion: June 3, 2021
• Study Completion: December 21, 2022
• Last Updated: April 25, 2023
• Results First Posted: April 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

US (5)