Gemcitabine Hydrochloride, Dasatinib, and Erlotinib Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
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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 Other: laboratory biomarker analysis |
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 |
- 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 ]
- Overall survival (OS) [ Time Frame: The time from enrollment until the time of death due to any cause, assessed up to 2 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 2 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 30 days after completion of study treatment ] [ 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 30 days after study treatment ] [ 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:
Drug: dasatinib
Given PO
Other Names:
Drug: erlotinib hydrochloride
Given PO
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
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 |
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 because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with erlotinib or dasatinib, 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 3A4 (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| United States, Tennessee | |
| Vanderbilt-Ingram Cancer Center | Recruiting |
| Nashville, Tennessee, United States, 37232 | |
| Contact: Dana B. Cardin 800-811-8480 | |
| Principal Investigator: Dana B. Cardin | |
| 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, GI 1173, CDR0000738551, P30CA068485 |
| Study First Received: | August 7, 2012 |
| Last Updated: | June 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Adenocarcinoma Adenocarcinoma, Mucinous Pancreatic Neoplasms Carcinoma, Acinar Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous 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 |
ClinicalTrials.gov processed this record on June 17, 2013