viernes, 8 de julio de 2016

NCT02349867 Clinical Trial - National Cancer Institute || Sorafenib Tosylate, Vorinostat, Gemcitabine Hydrochloride, and Radiation Therapy in Treating Patients with Pancreatic Cancer

NCT02349867 Clinical Trial - National Cancer Institute

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Sorafenib Tosylate, Vorinostat, Gemcitabine Hydrochloride, and Radiation Therapy in Treating Patients with Pancreatic Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IBiomarker/Laboratory analysis, TreatmentActive18 and overMCC-12-07328
NCI-2015-00017, NCT02349867

Trial Description


This phase I trial studies the side effects and best dose of sorafenib tosylate and vorinostat when given together with gemcitabine hydrochloride and radiation therapy in treating patients with pancreatic cancer. Sorafenib tosylate and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving sorafenib tosylate, vorinostat, gemcitabine hydrochloride, and radiation therapy may be a better treatment for pancreatic cancer.

Further Study Information

I. To determine the doses and schedule appropriate for phase 2 study of sorafenib (sorafenib tosylate) and vorinostat with concurrent gemcitabine (gemcitabine hydrochloride) and radiation therapy (RT) as neoadjuvant treatment of pancreatic cancer following chemotherapy.
I. To evaluate the safety and toxicity of concurrent chemoradiation using a regimen of sorafenib, vorinostat, gemcitabine, and RT following chemotherapy.
II. To observe the antitumor effects of this regimen.
III. To evaluate the percentage of patients able to undergo resection after neoadjuvant therapy (chemotherapy followed by concurrent chemoradiation).
IV. To calculate the R0 (complete removal of all tumor) resection rate following chemoradiation.
V. To evaluate progression-free survival (PFS).
VI. To evaluate overall survival (OS).
I. To assess the feasibility of analyzing pancreatic patient circulating tumor cells (CTCs) for enumeration and caspase 3 cleavage before and after concurrent chemoradiation.
II. To characterize pancreatic tumors (when sufficient tissue samples are available) for expression of cluster of differentiation (CD)95, myeloid cell leukemia (MCL)1, and platelet-derived growth factor receptor (PDGFR) by evaluating archived tumor tissue from diagnostic biopsies and comparing this to tissue obtained at the time of resection after chemoradiation.
OUTLINE: This is a dose escalation study of sorafenib tosylate and vorinostat.
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once weekly for 6 doses, and sorafenib tosylate orally (PO) twice daily (BID) and vorinostat PO once daily (QD) 3-5 days a week on days of radiation therapy for a total of 28 days over 5-6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo 3-dimensional conformal radiation therapy (3D CRT) or intensity-modulated radiation therapy (IMRT) on days 1-5 over 5 1/2 weeks for a total dose of 50.4 gray (Gy) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 2-3 months for up to 2 years.

Eligibility Criteria

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 fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX], fluorouracil/irinotecan/leucovorin calcium/oxaliplatin [FOLFIRINOX], or folinic acid-fluorouracil-irinotecan [FOLFIRI])
Candidate for additional therapy consisting of radiation with gemcitabine–radiosensitization
Able to initiate study treatment no later than 6 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; 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 administration (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 initiation 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
Persistent heart rate (HR) < 50 or > 120 beats per minute (bpm)
Corrected 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 60-100 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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Virginia Commonwealth University/Massey Cancer Center

  • National Cancer Institute
Andrew Poklepovic, Principal Investigator

Trial Sites


Virginia Commonwealth University/Massey Cancer Center
Andrew Poklepovic
Ph: 804-628-2321
Andrew Poklepovic
Principal Investigator
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the record via the link above for more information about participating sites.

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