- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01660971
Gemcitabine Hydrochloride, Dasatinib, and Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery
A Phase 1 Study of Gemcitabine, Dasatinib and Erlotinib in Patients With Advanced Pancreatic Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
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 30-60 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 glutamate 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 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
Patients may not have any clinically significant cardiovascular disease including the following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months
- Prolonged corrected QT (QTc) > 480 msec (Fridericia correction)
- Known ejection faction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (gemcitabine, dasatinib, erlotinib)
Patients receive gemcitabine hydrochloride IV over 30-60 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.
|
Given PO
Other Names:
Given PO
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose of gemcitabine hydrochloride and dasatinib given together with erlotinib hydrochloride, determined by incidence of dose-limiting toxicity graded according to NCI CTCAE v 4.0
Time Frame: Up to 4 weeks after completion of study treatment
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Up to 4 weeks after completion of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: The time from enrollment until the time of death due to any cause, assessed up to 6 years
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The OS curves will be estimated by the Kaplan-Meier method.
Median OS and its 95% confidence intervals will be estimated.
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The time from enrollment until the time of death due to any cause, assessed up to 6 years
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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
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The PFS curves will be estimated by the Kaplan-Meier method.
Median PFS and its 95% confidence intervals will be estimated.
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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
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Response rate, assessed according to RECIST
Time Frame: Up to 6 years
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The response rate and its 95% confidence interval will be calculated using the exact binominal method.
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Up to 6 years
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Response duration
Time Frame: The time from when measurement criteria are met for complete response or partial response (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented, assessed up to 6 years
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The response duration for the responders will be summarized using mean, median and standard deviation.
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The time from when measurement criteria are met for complete response or partial response (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented, assessed up to 6 years
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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
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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.
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Up to 30 days after completion of study treatment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dana B Cardin, Vanderbilt University/Ingram Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Carcinoma
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Erlotinib Hydrochloride
- Dasatinib
- Gemcitabine
Other Study ID Numbers
- NCI-2012-01290 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- VICCGI1173
- GI 1173 (Other Identifier: Vanderbilt University/Ingram Cancer Center)
- CDR0000738551
- 9043 (CTEP)
- P30CA068485 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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