Phase I-II to Evaluate Efficacy/Safety of Sorafenib+Gemcitabine+Radiotherapy in Locally Advanced Pancreatic Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00789763
Recruitment Status : Completed
First Posted : November 13, 2008
Last Update Posted : November 29, 2012
Information provided by (Responsible Party):
Grupo Espanol Multidisciplinario del Cancer Digestivo

Brief Summary:

Phase I: Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Gemcitabine and Radiotherapy

Phase II: Activity profile evaluating Progression-free rates (PFR) at 6 months, Response rate, Overall survival, Toxicity profile

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Gemcitabine Radiation: Radiotherapy Drug: Sorafenib Phase 1

Detailed Description:

Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Gemcitabine and Radiotherapy

Definition of maximum tolerated dose (MTD):

The MTD is defined as the highest dose level which can be given to 6 patients such that no more than 1 patient experiences a DLT .

Definition of Recommended Dose (DR):

Is the MTD

Definition of Dose-limiting toxicity (DLT):

DLT will be defined as any of the following occurring during the period of treatment and regarded as related to the combination regimen.

  • Grade 4 thrombocytopenia persisting greater than 4 days, or with bleeding requiring platelet transfusion
  • Grade 4 neutropenia lasting more than 7 days
  • Febrile neutropenia (≥ 38.5oC) with an absolute neutrophil count ≤ 1000/mm3
  • Any grade 3 or 4 non-hematologic toxicity related to the combination [occurring despite optimal supportive care, if applicable] except hyperglycemia, hypoglycemia, deep venous thrombosis, or hyperbilirubinemia secondary to stent malfunction.
  • Hypertension that is symptomatic and not managed by maximal use of three different classes of antihypertensives, or any episode of malignancy hypertension

(Detailed Dose Modifications and G-CSF use in case of febrile neutropenia will be outlined in the full protocol version)

Phase II

Primary objective:

Activity profile evaluating Progression-free rates (PFR) at 6 months

Secondary objective:

Response rate Overall survival Toxicity profile

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Multicentric Phase I-II Trial to Evaluate the Efficacy and Safety of the Combination of Sorafenib (BAY 43-9006), Gemcitabine and Concurrent Radiotherapy, in Locally Advanced Pancreatic Carcinoma
Study Start Date : December 2007
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Sorafenib + gemcitabine + radiotherapy Drug: Gemcitabine
300 mg/m2/one per week, i.v., during 5 weeks.
Radiation: Radiotherapy
1.8 Gy/day 5 days per week during 5 weeks (total dose 45Gy)
Drug: Sorafenib
200-800 mg/day p.o. during 5 weeks
Other Name: Brand name: nexavar

Primary Outcome Measures :
  1. SAFETY [ Time Frame: End of Study ]
  2. EFFICACY [ Time Frame: End of Study ]
  3. TO DETERMINE MTD [ Time Frame: Treatment (5 weeks) ]

Secondary Outcome Measures :
  1. RESPONSE (ACCORDING TO RECIST) [ Time Frame: End of Study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. -Patients with histological or cytological confirmed locally advanced pancreatic adenocarcinoma pancreatic carcinoma or metastatic pancreatic carcinoma for phase I.
  2. -Patients with measurable (according to RECIST) disease.
  3. -Male or female patients > or = 18 years old
  4. -ECOG 0-1
  5. -Adequate bone marrow, liver , and renal function: Absolute neutrophil count ( ANC) >= 1,500/mm3 Platelets> or = 100,000/µl Hemoglobin >=9.0 g/dl Total bilirubin < 1.5 x the upper limit of normal. ALT and AST <= 2.5 x upper limit of normal ( <= 5X upper limit of normal for patients with liver involvement ) Serum creatinine <= 1.5 times x the upper limit of normal. Patients with creatinine clearance >= 45mL/min PT( prothrombin time ) or INR( international normalized ratio ) and PTT ( partial thromboplastin time ) < =1.5 x
  6. -Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least six months after the last administration of sorafenib
  7. -Signed informed consent prior to any study specific procedures

Exclusion Criteria:

  1. -Patients with previous treatment for pancreatic carcinoma
  2. -PTV ( planning target volume ) >500 cm3 or 5 cm (maximum diameter)
  3. -Patients with known or suspected allergy to iodated contrasts or renal impairment which prevents from radiological tests.
  4. -Pregnant or nursing patients. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  5. -General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
  6. -Previous cancer that is distinct in primary site or histology from NSCLC except cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated > 3 years prior to study entry
  7. -Concurrent treatment with other experimental drugs (within 30 days prior to study entry).
  8. -Concurrent treatment with other anti-cancer therapy.
  9. -Therapeutic anticoagulation with Vitamin K antagonists such as warfarin or with heparins or heparinoids. Low dose warfarin is permitted if INR is <1.5 . Low dose aspirin is permitted .
  10. -Patients with any medical condition which could jeopardize their safety while his participation in the study .
  11. -Significant weight loss (> or equal 10% body weight during preceding 6 weeks)
  12. -Major surgery within 3 previous weeks, or laparoscopic biopsy or significant traumatic injury within 2 weeks of prior to first dose of study drug.
  13. -Known or suspected allergy to sorafenib or any agent given in the course of this trial .
  14. -Patients with evidence or history of bleeding diathesis or coagulopathy
  15. -Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
  16. -Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
  17. -Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina or new-onset angina (began within the last 3 months) or myocardial infarction within the last 6 months
  18. -Patients with Child-Pugh class C hepatic impairment
  19. -Patients with severe renal impairment (calculated creatinine clearance of < 30 ml/min) or who require dialysis
  20. -Active clinically serious infections > CTCAE Grade 2
  21. -Serious, non-healing wound, ulcer, or bone fracture
  22. -Patients with concomitant ketoconazole, itraconazole,ritonavir,rifampicin or St. John's Wort (Hypericum perforatum).
  23. -Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
  24. -Any instable condition that may interfere with the patients participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00789763

Hospital de La Santa Creu I Sant Pau
Barcelona, Spain, 08025
Hospital Clinic I Provincial
Barcelona, Spain, 08036
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario La Fe
Valencia, Spain, 46009
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo Identifier: NCT00789763     History of Changes
Other Study ID Numbers: GEMCAD 0701
First Posted: November 13, 2008    Key Record Dates
Last Update Posted: November 29, 2012
Last Verified: November 2012

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
pancreatic cancer
Pancreatic cancer locally advanced

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vitamin B Complex
Growth Substances