Gemcitabine Hydrochloride, Dasatinib, and Erlotinib Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01660971
First received: August 7, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and dasatinib when given together with erlotinib hydrochloride in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Dasatinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and dasatinib together with erlotinib hydrochloride may kill more tumor cells.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: gemcitabine hydrochloride
Drug: dasatinib
Drug: erlotinib hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Gemcitabine, Dasatinib and Erlotinib in Patients With Advanced Pancreatic Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of gemcitabine hydrochloride and dasatinib given together with erlotinib hydrochloride, determined by incidence of dose-limiting toxicity (DLT) graded according to NCI CTCAE v 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: The time from enrollment until the time of death due to any cause, assessed up to 6 years ] [ Designated as safety issue: No ]
    The OS curves will be estimated by the Kaplan-Meier method. Median OS and its 95% confidence intervals will be estimated.

  • Progression free survival (PFS) [ Time Frame: The time from enrollment until the first occurrence of radiographic or clinical evidence of disease progression or death due to any cause, assessed up to 6 years ] [ Designated as safety issue: No ]
    The PFS curves will be estimated by the Kaplan-Meier method. Median PFS and its 95% confidence intervals will be estimated.

  • Response rate, assessed according to RECIST [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    The response rate and its 95% confidence interval will be calculated using the exact binominal method.

  • Response duration [ Time Frame: The time from when measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented, assessed up to 6 years ] [ Designated as safety issue: No ]
    The response duration for the responders will be summarized using mean, median and standard deviation.

  • Serious and other significant adverse events (AEs), graded according to NCI CTCAE v 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    The patient incidence of AEs will be summarized by preferred term, severity and relationship to study drug. Cross tabulations will be provided to summarize frequencies of abnormalities.


Estimated Enrollment: 24
Study Start Date: July 2012
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gemcitabine, dasatinib, erlotinib)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and dasatinib PO QD and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (also phase II recommended dose) of the combination of gemcitabine (gemcitabine hydrochloride), erlotinib (erlotinib hydrochloride) and dasatinib in patients with advanced pancreatic adenocarcinoma.

SECONDARY OBJECTIVES:

I. To determine the safety profile of the combination of gemcitabine, erlotinib and dasatinib.

II. To evaluate the response rate and response duration of advanced pancreatic adenocarcinoma treated with dasatinib, erlotinib and gemcitabine.

III. To determine progression-free survival and overall survival for this group of patients.

IV. To determine the utility of advanced magnetic resonance imaging techniques to assess in vivo effects of therapy (changes in tumor vascularity, cellularity).

V. To assess the use of serum markers as predictors of response and outcome.

OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and dasatinib.

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and dasatinib orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 4 weeks thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cytologically or histologically confirmed pancreatic adenocarcinoma (excluding islet cell or ampullary tumors) that is metastatic or unresectable
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients may have received prior chemotherapy for advanced disease as long as it did not include gemcitabine; if patients received prior adjuvant therapy including gemcitabine, patients must be > 6 months from the last dose of gemcitabine; patients must have recovered from side effects of prior therapy to grade =< 1 as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
  • Patients may have received prior radiation presuming > 4 weeks since last dose and measurable disease outside the radiation field
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Anticipated life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin < 2.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic pyruvate transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal OR =< 5 X institutional upper limit of normal when liver metastases are present
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients must be able to swallow pills

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (with the exception of alopecia and neuropathy); no radiation is allowed on study
  • Patients who are receiving any other investigational agents
  • Major surgical procedure within 4 weeks of treatment
  • Patients with known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib, erlotinib or gemcitabine
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study, breastfeeding should be discontinued if the mother is treated with erlotinib or dasatinib
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy and are thus excluded
  • Patients on potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and inhibitors
  • Malabsorption syndrome or other condition that would interfere with intestinal absorption
  • Other active malignancy (with the exception of locally treated non-melanoma skin cancers)
  • Human immunodeficiency virus (HIV) positive patients who are on combination antiretroviral therapy
  • Myocardial infarction or ventricular tachyarrhythmia within 6 months
  • Prolonged corrected QT interval (QTc) > 480 msec (Fridericia correction)
  • Known ejection faction less than institutional normal
  • Major conduction abnormality (unless a cardiac pacemaker is present)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01660971

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Dana B. Cardin    615-936-6925    dana.cardin@vanderbilt.edu   
Principal Investigator: Dana B. Cardin         
Sponsors and Collaborators
Investigators
Principal Investigator: Dana Cardin Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01660971     History of Changes
Other Study ID Numbers: NCI-2012-01290, NCI-2012-01290, CDR0000738551, VICCGI1173, GI 1173, 9043, P30CA068485
Study First Received: August 7, 2012
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma, Acinar Cell
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
Gemcitabine
Erlotinib
Dasatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014