A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB IN METASTATIC COLORECTAL CANCER PATIENTS RECEIVING IRINOTECAN, 5-FLUOROURACIL AND LEUCOVORIN (FOLFIRI) AS FIRST LINE TREATMENT

• Register: EUCTR
• Last refreshed on: 11 February 2013
• Main ID: EUCTR2007-000325-21-GB
• Date of registration: 26/11/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. - 235 East 42nd Street - New York - 10017
• Public title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB IN METASTATIC COLORECTAL CANCER PATIENTS RECEIVING IRINOTECAN, 5-FLUOROURACIL AND LEUCOVORIN (FOLFIRI) AS FIRST LINE TREATMENT
• Scientific title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB IN METASTATIC COLORECTAL CANCER PATIENTS RECEIVING IRINOTECAN, 5-FLUOROURACIL AND LEUCOVORIN (FOLFIRI) AS FIRST LINE TREATMENT
• Date of first enrolment: 07/04/2008
• Target sample size: 720
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000325-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: FOLFIRI Regimen

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Germany, Hungary, Ireland, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient must have histologically- or cytologically-confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies.
2. Patient must have at least one measurable lesion as defined by RECIST criteria.
3. Patient has not previously received therapy for metastatic colorectal disease but for whom FOLFIRI treatment is clinically indicated.
4. Patient may have received adjuvant therapy for primary colorectal cancer, provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented.
5. Age =18 years.
6. (ECOG) Performance status = 1
7. Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =2.5 x upper limit of normal (ULN), or AST and ALT =5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin =1.5 x ULN
• Serum albumin =3.0 g/dL
• Absolute neutrophil count (ANC) =1500/mm3
• Platelets =100,000/mm3
• Hemoglobin =9.0 g/dL
• Serum creatinine =1.5 x ULN
8. Signed and dated informed consent document indicating that the patient or legally
acceptable representative has been informed of all the pertinent aspects of the trial prior to enrollment.
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
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. History of another primary malignancy =3 years, with the exception of non-melanoma skin cancer and in situ carcinoma of the uterine cervix.
2. Current, recent, or planned participation in an experimental treatment drug study other than this protocol.
3. Prior treatment with a VEGF, VEGFR or RTK inhibitor, or prior enrollment on this
study.
4. Treatment with potent CYP3A4 inhibitor within 7 days of sunitinib/placebo dosing or with potent CYP3A4 inducer within 12 days of sunitinib/placebo dosing.
5. Prior full field radiotherapy = 4 weeks, or limited field radiotherapy, =to 2 weeks prior to study enrollment. Or previous radiation treatment >30% of the bone marrow (Appendix 7). Patients treated with palliative radiotherapy must have measurable metastatic disease outside the irradiation fields.
6. Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks before starting treatment; anticipation of need for major surgical procedure (e.g., impending bowel obstruction) during the course of the study.
7. Female patients who are pregnant or lactating or men and women of reproductive
potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 90 days after
discontinuing study treatment. Adequate contraception is defined as double barrier
contraception (ie, condom plus spermicide in combination with a female condom,
diaphragm, cervical cap or intrauterine device).
8. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition as irinotecan, 5-FU, or leucovorin.
9. History or presence of brain metastases, spinal cord compression, carcinomatous
meningitis, or leptomeningeal disease.
10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment, unless affected area has been removed surgically.
11. Patients with unresolved bowel obstruction or chronic diarrhoea.
12. Any of the following within the 12 months prior to study enrollment: myocardial
infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischaemic attack, pulmonary embolus, peptic ulcer disease, infectious or inflammatory bowel disease, diverticulitis, deep vein thrombosis, or other significant thromboembolic event.
13. Ongoing cardiac dysrhythmias of NCI CTCAE grade =? 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females.
14. Hypertension that cannot be controlled by medication (>150/100 mmHg) despite optimal medical therapy.
15. Current treatment with therapeutic doses of anticoagulant medication (low dose warfarin or equivalent up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
16. History of clinically significant bleeding within the past 6 months, including gross
hemoptysis or haematuria, or underlying coagulopathy.
17. Active infection, or on antiretroviral therapy for HIV disease.
18. History of other medical or psychiatric condition, metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

first-line treatment of patients with metastatic colorectal cancer.
MedDRA version: 9.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer

Intervention(s)

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-0011248
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 12.5-50
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: CAMPTO
Product Name: CAMPTO
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Irinotecan Hydrochloride
CAS Number: 100286-90-6
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 40mg/2ml-100mg/5ml

Trade Name: Fluorouracil
Product Name: Fluorouracil
Pharmaceutical Form: Solution for injection
INN or Proposed INN: 5-FU
CAS Number: 51-21-8
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 25 mg/ml-50 mg/ml

Trade Name: Leucovorin
Product Name: Leucovorin
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Calcium Folinate
CAS Number: 1492-18-8
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 3 mg/mL-10 mg/mL

Primary Outcome(s)

Main Objective: To demonstrate that the combination of FOLFIRI plus sunitinib is superior to FOLFIRI
plus placebo in prolonging the progression-free survival (PFS) in the first-line treatment of patients with metastatic colorectal cancer.

Primary end point(s): Progression-free survival (PFS)

Secondary Objective: • To compare the overall survival (OS) in patients randomized to FOLFIRI plus sunitinib versus that in patients randomized to FOLFIRI plus placebo.
• To compare the objective response rate (ORR) and duration of response (DR) in patients randomized to FOLFIRI plus sunitinib versus that in patients randomized to FOLFIRI plus placebo.
• To evaluate the safety and tolerability of sunitinib in combination with FOLFIRI.
• To compare patient reported symptoms with the MDASI-GI.
• To compare patient-reported outcomes as measured by the EuroQoL EQ-5D Self-Report Questionnaire (EQ-5D)

Secondary ID(s)

A6181122

2007-000325-21-SE