- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02349867
Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer
A Phase 1 Study of Neoadjuvant Chemotherapy, Followed by Concurrent Chemoradiation With Gemcitabine, Sorafenib, and Vorinostat in Pancreatic Cancer
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Virginia
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adenocarcinoma of the pancreas
- Prior therapy with ≥ 1 prior systemic therapy over a period of at least 2 months (eg, at least two 4-week cycles of a regimen such as gemcitabine and nab-paclitaxel; or at least four 2-week cycles of a regimen such as FOLFOX, FOLFIRINOX, or FOLFIRI) -Candidate for additional therapy consisting of radiation with gemcitabine- radiosensitization.
- Able to initiate study treatment no later than 9 weeks from last dose of any antineoplastic component of prior therapy regimen.
- Recovery from ≥ grade 2 toxicities of prior therapy regimen to grade 1 or baseline, with the exception of anemia and lymphopenia and chronic residual toxicities that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profiles of gemicitabine, sorafenib, and vorinostat (eg, alopecia, changes in pigmentation, stable endocrinopathies). Patients with ≤ grade 2 peripheral sensory or motor neuropathy are eligible..
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 x upper limit of normal (ULN) for the laboratory
- Total bilirubin <= 1.5 x ULN for the laboratory at the time of enrollment, all forms of biliary stents allowed
- Creatinine clearance >= 45 mL/min as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine and gender
- International normalized ratio (INR) <= 1.5
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelets >= 100,000/mm^3 (may not be transfused to meet this level for enrollment)
- Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) (version [v]1.1
- Ability to understand and the willingness to sign a written informed consent document
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use a medically accepted form of birth control during the treatment and for 2 months following completion of study treatment
Exclusion Criteria:
- Prior radiotherapy for pancreatic cancer
- Prior surgical resection of pancreatic cancer
- Evidence of metastatic disease
- Any investigational agent within 4 weeks of study treatment initiation
- Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
Intolerance of protocol agents as follows:
- Known or presumed intolerance of gemcitabine, vorinostat or sorafenib
- Experienced any of the following toxicities with prior gemcitabine adminstration (if given): capillary leak syndrome, posterior reversible encephalopathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, unexplained dyspnea or other evidence of severe pulmonary toxicity, or severe hepatic toxicity
- Unable to swallow medication
- Suspected malabsorption or obstruction; note: use of pancreatic enzyme supplements is allowed to control malabsorption
Contraindication to antiangiogenic agents, including:
- Bronchopulmonary hemorrhage/bleeding event >= grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] v4.0) within 12 weeks prior to of treatment
- Any other hemorrhage/bleeding event >= grade 3 (CTCAE v4.0) within 12 weeks prior to initiation of treatment
- Serious non-healing wound, ulcer, or bone fracture
- Arterial thrombotic or embolic events such as a myocardial infarction or cerebrovascular accident (including transient ischemic attacks) within the 6 months prior to initiation of treatment. Incidental clinically insignificant embolic phenomena that do not require anti-coagulants are not excluded. Also,tumor-associated thrombus of locally-involved vessels does not count as an exclusion criterion.
- Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease
- Concomitant use of other histone deacetylase (HDAC) inhibitors
- Planned ongoing administration of STRONG cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers. Examples of clinical inducers and classifications of strong, moderate, and weak interactions are available through the FDA website (Table 3-3 of website): http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
- Persistent heart rate (HR) < 50 or > 120 beats per minute (bpm).
QT(c) ≥ 481 ms (>= grade 2) on electrocardiogram (ECG) prior to initiation of treatment
If baseline QTc on screening ECG meets exclusion criteria:
- Check potassium and magnesium serum levels
- Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc
- For patients with HR >60 of >100 beats per minute (bpm), no manual read of QTc is required
- For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine QTc
Planned ongoing treatment with other drugs thought to potentially adversely interact with study drugs; if such medications have been used, patients must be off of these agents for >= 2 weeks prior to initiation of treatment:
- Anticoagulants at therapeutic doses
- Immunosuppressants such as tacrolimus, leflunomide or tofacitinib, roflumilast, pimecrolimus
- Serious uncontrolled infection > grade 2 (CTCAE v4.0)
- Medical, psychological, or social conditions that, in the opinion of the investigator, may increase the patient's risk or interfere with the patient's participation in the study or hinder evaluation of the study results
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (chemotherapy, chemoradiation)
Participants receive gemcitabine IV infusion over 30 minutes (200 mg/m2 weekly) x 6, concurrent administration of oral sorafenib and oral vorinostat (both per dose-escalation schema), and concurrent RT( 3-Dimensional Conformal Radiation Therapy or Intensity-Modulated Radiation Therapy) administered at 1.8-Gy fractions to a total dose of 50.4 Gy over 5 ½ weeks (28 daily fractions).
|
Given IV
Other Names:
Undergo IMRT
Other Names:
Undergo 3D CRT
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Circulating tumor cells (CTCs) will be captured and analyzed, when detected.
Pancreatic cancer has been a difficult tumor in which to detect CTCs (41).
Utilization of techniques that do not require cell surface marker expression will be explored.
Samples will either be analyzed by negative-selection techniques (RosetteSep).
Peripheral blood samples will be collected at several time-points for CTC enumeration and to evaluate CD95 density.
Other Names:
Circulating tumor cells (CTCs) will be captured and analyzed, when detected.
Pancreatic cancer has been a difficult tumor in which to detect CTCs (41).
Utilization of techniques that do not require cell surface marker expression will be explored.
Samples will either be analyzed by with the ApoStream dielectrophoretic field-flow fractionation (DEPfff) enrichment device.
Peripheral blood samples will be collected at several time-points for CTC enumeration and to evaluate CD95 density.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended phase 2 dose and schedule
Time Frame: 18-36 months
|
Determine the doses and schedule appropriate for phase 2 study of sorafenib and vorinostat with concurrent gemcitabine and radiation therapy (RT) as neoadjuvant treatment of pancreatic cancer following chemotherapy.
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18-36 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events using National Cancer Institute CTCAE v4.0
Time Frame: Up to 30 days following last administration of the chemoradiation treatment
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Adverse events using NCI Common Terminology Criteria for Adverse Events, Version 4.0.
Adverse events will be listed and summary descriptive statistics will be calculated.
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Up to 30 days following last administration of the chemoradiation treatment
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Tumor response (complete response or partial response) measured using RECIST version 1.1
Time Frame: Up to 2 years
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Evaluate number of participants with tumor response measured using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
At the completion of concurrent chemoradiation.
Tumor response will be measured as complete response, partial response, stable disease, or tumor progression.
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Up to 2 years
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Surgery
Time Frame: Up to 2 years
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Number of participants able to undergo resection after neoadjuvant therapy (chemotherapy followed by concurrent chemoradiation)
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Up to 2 years
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R0 Resection rate
Time Frame: Up to 2 years
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Determine the number of patients able to undergo margin-negative resection following neoadjuvant therapy.
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Up to 2 years
|
Progression-free survival (PFS)
Time Frame: Up to 2 Years
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Number of participants with progression free survival (PFS) defined as the percentage of patients able to undergo margin-negative resection following neoadjuvant therapy
|
Up to 2 Years
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Overall Survival
Time Frame: Up to 2 Years
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The number of participants with overall survival (OS) defined as the time from the date of diagnosis until death by any cause
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Up to 2 Years
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
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
- Neoplasms by Site
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Pancreatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Histone Deacetylase Inhibitors
- Gemcitabine
- Sorafenib
- Vorinostat
Other Study ID Numbers
- MCC-12-07328 (OTHER: Virginia Commonwealth University/Massey Cancer Center)
- P30CA016059 (U.S. NIH Grant/Contract)
- NCI-2015-00017 (REGISTRY: CTRP (Clinical Trial Reporting Program))
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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