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

Sponsor

Grupo Espanol Multidisciplinario del Cancer Digestivo (Other)

Overall Status

Completed

CT.gov ID

NCT00789763

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

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 :

Dec 1, 2007

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

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 Names: Brand name: nexavar

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 Names:

Brand name: nexavar

Outcome Measures

Primary Outcome Measures

SAFETY [End of Study]
EFFICACY [End of Study]
TO DETERMINE MTD [Treatment (5 weeks)]

Secondary Outcome Measures

RESPONSE (ACCORDING TO RECIST) [End of Study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

-Patients with histological or cytological confirmed locally advanced pancreatic adenocarcinoma pancreatic carcinoma or metastatic pancreatic carcinoma for phase I.
-Patients with measurable (according to RECIST) disease.
-Male or female patients > or = 18 years old
-ECOG 0-1
-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
-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
-Signed informed consent prior to any study specific procedures

Exclusion Criteria:

-Patients with previous treatment for pancreatic carcinoma
-PTV ( planning target volume ) >500 cm3 or 5 cm (maximum diameter)
-Patients with known or suspected allergy to iodated contrasts or renal impairment which prevents from radiological tests.
-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
-General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
-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
-Concurrent treatment with other experimental drugs (within 30 days prior to study entry).
-Concurrent treatment with other anti-cancer therapy.
-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 .
-Patients with any medical condition which could jeopardize their safety while his participation in the study .
-Significant weight loss (> or equal 10% body weight during preceding 6 weeks)
-Major surgery within 3 previous weeks, or laparoscopic biopsy or significant traumatic injury within 2 weeks of prior to first dose of study drug.
-Known or suspected allergy to sorafenib or any agent given in the course of this trial .
-Patients with evidence or history of bleeding diathesis or coagulopathy
-Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
-Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
-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
-Patients with Child-Pugh class C hepatic impairment
-Patients with severe renal impairment (calculated creatinine clearance of < 30 ml/min) or who require dialysis
-Active clinically serious infections > CTCAE Grade 2
-Serious, non-healing wound, ulcer, or bone fracture
-Patients with concomitant ketoconazole, itraconazole,ritonavir,rifampicin or St. John's Wort (Hypericum perforatum).
-Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
-Any instable condition that may interfere with the patients participation in the study

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital de La Santa Creu I Sant Pau	Barcelona	Spain	08025
2	Hospital Clinic I Provincial	Barcelona	Spain	08036
3	Hospital Universitario La Paz	Madrid	Spain	28046
4	Hospital Universitario La Fe	Valencia	Spain	46009