Know Cancer

forgot password

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

Phase 1
18 Years
Not Enrolling
Pancreatic Cancer

Thank you

Trial Information

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

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Time Frame:

End of Study

Safety Issue:



Spain: Spanish Agency of Medicines

Study ID:




Start Date:

December 2007

Completion Date:

January 2012

Related Keywords:

  • Pancreatic Cancer
  • pancreatic cancer
  • Pancreatic cancer locally advanced
  • Carcinoma
  • Pancreatic Neoplasms