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Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02194829
First Posted: July 18, 2014
Last Update Posted: December 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This partially randomized phase I/II trial studies the side effects and best dose of WEE1 inhibitor MK-1775 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 MK-1775 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 MK-1775 in treating patients with pancreatic cancer.

Condition Intervention Phase
Metastatic Pancreatic Adenocarcinoma Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Unresectable Pancreatic Carcinoma Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Drug: Nab-paclitaxel Other: Pharmacological Study Other: Placebo Drug: WEE1 Inhibitor AZD1775 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I and Randomized Phase II Study of Nab-Paclitaxel/Gemcitabine With or Without AZD1775 for Treatment of Metastatic Adenocarcinoma of the Pancreas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of WEE1 inhibitor MEK-1775, defined as the highest dose level at which < 33% of 6 patients experience a dose-limiting toxicity graded according to Common Terminology Criteria for Adverse Events version 4 (Phase I) [ Time Frame: 4 weeks ]
  • Progression-free survival [ Time Frame: From randomization to documented progression or death without progression, assessed up to 2 years ]
    PFS by arm will be compared using one-sided log-rank tests. Cox's proportional hazards models will be used to estimate hazard ratios.


Secondary Outcome Measures:
  • Disease control rate (CR + PR + SD) [ Time Frame: Up to 2 years ]
    Will be analyzed using Fisher's exact tests at a one-sided significance level of 0.15.

  • Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 2 years ]
    OS by arm will be compared using one-sided log-rank tests. Cox's proportional hazards models will be used to estimate hazard ratios.

  • Response rate (CR + PR) [ Time Frame: Up to 2 years ]
    Will be analyzed using Fisher's exact tests at a one-sided significance level of 0.15.


Other Outcome Measures:
  • Accuracy of change in tumor FDG uptake (SUVmax) between baseline FDG-PET and week 4 FDG-PET as a predictor of progression-free survival [ Time Frame: Up to week 4 ]
    Time-dependent receiver operator characteristic methodology will be used to assess the ability of SUVmax change to predict PFS.

  • Change in tumor FDG uptake (SUVmax) [ Time Frame: Baseline to week 4 ]
    Will be evaluated as a predictor of response using RECIST as the reference standard.

  • Change in tumor FDG uptake (SUVmax) between baseline FDG-PET and week 4 FDG-PET [ Time Frame: Baseline to week 4 ]
    Will be compared between the patients from treatment arms C and D only as a continuous variable using Wilcoxon test and as binary variable (defined as summed SUVmax change from baseline < -25% versus >= -25%) using Fisher's exact tests.

  • Change in tumor FLT uptake (SUVmax) [ Time Frame: Baseline to 24 hours after initiation of treatment ]
    Will be compared between patients from treatment arms C and D.

  • Incidence of abrogation of early increase in tumor FLT uptake after initiation of treatment [ Time Frame: Up to 24 hours ]
  • Incidence of an early increase in tumor FLT uptake (FLT-flare) within 24 hours after initiation of treatment [ Time Frame: Up to 24 hours after initiation of treatment ]

Estimated Enrollment: 133
Actual Study Start Date: July 1, 2014
Estimated Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (phase I, dose level 1)
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 MK-1775 PO daily on days 1, 2, 8, 9, 15, and 16.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel
Other: Pharmacological Study
Correlative studies
Drug: WEE1 Inhibitor AZD1775
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775
Experimental: Arm B (phase I, dose level 2)
Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor MK-1775 as in Arm A.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel
Other: Pharmacological Study
Correlative studies
Drug: WEE1 Inhibitor AZD1775
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775
Active Comparator: Arm C (phase II, placebo)
Patients receive paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride as in Arm A. Patients also receive placebo PO daily on days 1, 2, 8, 9, 15, and 16.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel
Other: Pharmacological Study
Correlative studies
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Experimental: Arm D (phase II, WEE1 inhibitor MK-1775)
Patients receive paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and WEE1 inhibitor MK-1775 (recommended phase II dose) as in Arm A.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel
Other: Pharmacological Study
Correlative studies
Drug: WEE1 Inhibitor AZD1775
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PHASE I STUDY -- ARM A (DOSE LEVEL 1) AND ARM B (DOSE LEVEL 2)
  • Patients must have histologically or cytologically confirmed metastatic or unresectable locally advanced adenocarcinoma of the pancreas with no prior systemic therapy for metastatic or locally advanced disease
  • Previous neo-adjuvant or adjuvant treatment is allowed provided that it was given >= 6 months prior to registration
  • Patients must NOT be receiving any other investigational agents concurrently and must not have received any other investigational agents =< 4 weeks prior to registration
  • Patients must not have a pre-existing > grade 1 motor or sensory neuropathy
  • Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, gemcitabine or AZD1775
  • Patients must have 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 NOT be taking current medications or substances that are inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4)
  • Patients must NOT have 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) are not eligible if cluster of differentiation (CD)4 count is =< 200 cell/mm^3 or if receiving antiretroviral therapy
  • Patients must be able to swallow capsules whole
  • Patients must NOT have 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
  • Patients must be able to tolerate computed tomography (CT), magnetic resonance imaging (MRI) or PET imaging including contrast agents
  • Women must not be 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)
  • 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)
  • RANDOMIZED PHASE II STUDY -- ARMS C AND D
  • PHASE II: Patients must have histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas with no prior systemic therapy for metastatic disease
  • PHASE II: Patients must NOT have locally advanced disease
  • PHASE II: Patients must have measurable disease outside of the primary tumor (pancreas) by RECIST 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks prior to randomization
  • PHASE II: Previous neo-adjuvant or adjuvant treatment is allowed provided that there was no evidence of recurrent disease for at least 6 months after completion of neo-adjuvant/adjuvant treatment
  • PHASE II: Patients may have had prior radiotherapy for metastatic disease as long as it was > 4 weeks prior to randomization and the patient has recovered from adverse events associated with the radiotherapy
  • PHASE II: Patients must NOT be taking current medications or substances that are inhibitors or inducers of CYP3A4
  • PHASE II: Patients must NOT have received prior Wee1 inhibitors or AZD1775
  • PHASE II: Patients must NOT have received gemcitabine or nab-paclitaxel in a metastatic setting
  • PHASE II: Patients must NOT be receiving any other investigational agents concurrently and must not have received any other investigational agents =< 4 weeks prior to randomization
  • PHASE II: Patients must not have a pre-existing > grade 1 motor or sensory neuropathy
  • PHASE II: Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, gemcitabine or AZD1775
  • PHASE II: Patients must have ECOG performance status of 0 or 1
  • PHASE II: Patients must have a life expectancy of >= 12 weeks
  • PHASE II: Patients must NOT have 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
  • PHASE II: Patients must be able to swallow capsules whole
  • PHASE II: Patients with biliary stents are allowed
  • PHASE II: Patients must NOT have 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
  • PHASE II: Patients must be able to tolerate CT, MRI or PET imaging including contrast agents
  • PHASE II: Women must not be pregnant or breast-feeding

    • Females of childbearing potential must have a blood test or urine study within 5 days prior to randomization 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)
  • PHASE II: 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
  • PHASE II: Leukocytes >= 3,000/mcL
  • PHASE II: Absolute neutrophil count >= 1,500/mcL
  • PHASE II: Hemoglobin >= 9 g/dL
  • PHASE II: Platelets >= 100,000/mcL
  • PHASE II: Total bilirubin =< 1.5 institutional upper limit of normal (ULN)
  • PHASE II: AST (SGOT)/ALT (SGPT) =< 3 X institutional upper limit of normal (ULN) or =< 5 X ULN if the patient has liver metastases
  • PHASE II: 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)
  • PHASE II: For participation in the imaging research studies, patients must meet the additional following criteria:
  • PHASE II: The patient is participating in the trial at an institutional which has agreed to perform the imaging research studies, completed the American College of Radiation Imaging Network (ACRIN) defined scanner qualification procedures and received ACRIN approval
  • PHASE II: The patient has consented in writing to participate in one of the imaging research studies
  • PHASE II: The patient meets the criteria required for the imaging study in which the site is participating:

    • NOTE: Eligibility for participating in either imaging sub-study will depend on the availability of the imaging sub-study at a particular institution
    • For participation in the FDG-PET sub-study:

      • Patients must NOT have poorly controlled diabetes (defined as fasting glucose level >= 200 mg/dL) despite efforts to improve glucose control by fasting duration and adjustment of medications
      • Patient must NOT weigh more than the maximum weight limit for the PET table
      • Patients must have an evaluable lesion of > 20 mm in size on standard practice imaging study as assessed by site (either primary pancreas mass or metastasis)
    • For participation in the FLT-PET sub-study:

      • Patients must be able to lie still for a 1.5 hour PET scan.
      • Patient must NOT have a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-fluorothymidine
      • Patient must NOT weigh more than the maximum weight limit for the PET table
      • Patients must have an evaluable lesion in the pancreas > 20 mm in size on standard practice imaging study as assessed by site (lesion must be likely primary adenocarcinoma of the pancreas that is not primarily fibrotic or mucinous in nature)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02194829


Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jennifer Eads ECOG-ACRIN Cancer Research Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02194829     History of Changes
Other Study ID Numbers: NCI-2014-01425
NCI-2014-01425 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E1213
EA2131 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA2131 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: July 16, 2014
First Posted: July 18, 2014
Last Update Posted: December 12, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs