A randomized, double-blind phase 3 study of gemcitabine plus AG-013736 versus gemcitabine plus placebo for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer

• Conditions: nresectable or metastatic pancreatic cancer; MedDRA version: 9.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastatic; MedDRA version: 9.1Level: LLTClassification code 10033606Term: Pancreatic cancer non-resectable

• Registration Number: EUCTR2007-001568-66-HU
• Lead Sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-24
• Last Update Posted: 29 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 596

Inclusion Criteria

1. Histologically or cytologically confirmed, metastatic or locally-, advanced pancreatic adenocarcinoma not amenable to curative resection. Radiologically measurable disease is not required. Patients with documented invasion of adjacent organs (eg, colon, duodenum, stomach) by MRI/CT scan are not eligible.

2. Adequate hepatic and renal function documented within 14 days prior to treatment as documented by:
- AST and ALT =2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT =5.0 x ULN
- Total bilirubin =1.0 x ULN
- Serum creatinine =1.5 x ULN or calculated creatinine clearance =60 mL/min
- Urinary protein <1+ by urine dipstick. If dipstick is =1+ then a 24 hour urine collection should be done and the patient may enter only if urinary protein is <2 grams per 24 hours

3. Adequate bone marrow function as defined by:
- ANC =1500 cells/mm3
- platelets =100,000 cells/mm3
- hemoglobin =9 g/dL (which may be obtained by transfusion or growth factor support)

4. Male or female, age =18 years.

5. ECOG performance status of 0 or 1

6. Life expectancy of =12 weeks

7. Resolution of all acute toxic effects of prior radiotherapy, or surgical procedure to NCI CTCAE Grade =1. For patients having received prior elective surgery, study treatment should not be administered until surgical incision is fully healed

8. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.

9. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.

10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.

11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of patient reported outcome (PRO) measures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior treatment with any systemic chemotherapy for metastatic disease.

2. Prior adjuvant chemotherapy or radiotherapy <4 weeks before starting the study treatment. (Prior radiation therapy, with or without a radio-sensitizing dose of fluoropyrimidines, is allowed provided the patient has either measurable or non measurable disease outside the radiation port.)

3. Prior treatment with gemcitabine, AG-013736, or other VEGF inhibitors (eg, bevacizumab) in the adjuvant or metastatic setting.

4. Current or recent (within 1 month) use of a thrombolytic agent.

5. Central lung lesions involving major blood vessels (arteries or veins). Central lesions that maintain the structural integrity of vessels have the potential to bleed if the tumor lesion undergoes necrosis. MRI or CT angiography should be used in any case where there is any question as to whether blood vessels are involved.

6. History of hemoptysis > ½ tsp of bright red blood per day within past 1 week.

7. Gastrointestinal abnormalities including:
- inability to take oral medication
- requirement for intravenous alimentation
- prior surgical procedures affecting absorption including gastric resection
- treatment for active peptic ulcer disease in the past 6 months
- active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
- malabsorption syndromes

8. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine).

9. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John’s wort). Patients who need to be on anticoagulant therapy during treatment should be treated with low molecular weight heparin as the preferred therapy. The administration of coumadin may be allowed; however, due to possibility of inhibition of CYP1A2-mediated metabolism of coumadin by AG-013736, appropriate monitoring of prothrombin time/international normalized ratio (PT/INR) should be performed for any potential increased coumadin effect.

10. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.

11. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.

12. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism.

13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

14. History of a malignancy (other than pancreatic cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years

15. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of treatment. (Also

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified