Clinical trial NCT00569790: Phase II Trial of Combination Therapy With Irinotecan, S-1, and Bevacizumab (IRIS/Bev) in Patients With Unresectable or Recurrent Colorectal Cancer
Official title: Phase II Trial of Combination Therapy With Irinotecan, S-1, and Bevacizumab (IRIS/Bev) in Patients With Unresectable or Recurrent Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: S-1
Irinotecan
Bevacizumab
Lead sponsor: Taiho Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2007-12-07
Enrollment: 53
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether irinotecan, S-1, and bevacizumab are safe in the treatment of unresectable or recurrent colorectal cancer


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed colorectal carcinoma with inoperable, locally advanced, or metastatic disease, not amenable to curative therapy
2. Measurable disease or non-measurable but assessable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
3. Patients with no previous treatment (radiotherapy or chemotherapy). Patients who have received postoperative adjuvant chemotherapy are eligible if relapse is diagnosed more than 180 days after the end of such treatment.
4. Age ≥20 years
5. Life expectancy of at least 3 months
6. ECOG PS of 0 or 1
7. Adequate function of major organs as defined below:

   1. Hemoglobin ≥9.0g/dL
   2. White blood cell count ≥3,500/mm3
   3. Neutrophil count ≥1,500/mm3
   4. Platelet count ≥100,000/mm3
   5. Total bilirubin ≤1.5 mg/dL
   6. AST and ALT ≤100 U/L (\<200 U/L in patients with liver metastasis)
   7. Serum creatinine ≤1.2 mg/dL
   8. Creatinine clearance estimate by the Cockcroft-Gault method \>50 mL/min (reduce initial dosage by one step if ≥50 but \<80 mL/min)
8. Able to take capsules orally.
9. No electrocardiographic abnormalities within 28 days before enrollment that would clinically preclude the execution of the study, as judged by the investigator.
10. Voluntary written informed consent.

Exclusion Criteria:

1. Serious drug hypersensitivity or a history of drug allergy
2. Active double cancer
3. Active infections (e.g., patients with pyrexia of 38℃ or higher)
4. History of gastrointestinal perforation, intestinal tract paralysis, or ileus within 1 year.
5. Uncontrolled hypertension
6. Serious complications (e.g., pulmonary fibrosis, interstitial pneumonitis, heart failure, renal failure, hepatic failure, or poorly controlled diabetes)
7. Moderate or severe ascites or pleural effusion requiring treatment
8. Watery diarrhea
9. Treatment with flucytosine or atazanavir sulfate
10. Metastasis to the CNS
11. Pregnant women, possibly pregnant women, women wishing to become pregnant, and nursing mothers. Men who are currently attempting to conceive children.
12. Severe mental disorder
13. Continuous treatment with steroids
14. Urine dipstick for proteinuria should be \<2+
15. Patient with a past history of thrombosis, cerebral infarction, myocardial infarction, or pulmonary embolism
16. Major surgical procedure, open biopsy, or clinically significant traumatic injury within 4 weeks
17. Long-term daily treatment with aspirin (\>325 mg/day)
18. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
19. Judged ineligible for participation in the study by the investigator for safety reasons.

Primary outcomes:
measure: Safety
timeFrame: any time
Secondary outcomes:
measure: Progression-free survival, Response rate, Overall survival, Treatment situation
timeFrame: every course for first three courses, then every other course
Other outcomes:
Locations:
city: Sapporo
country: Japan
facility: Hokkaido University Hospital (Hokkaido Gastrointestinal Cancer Study Group)
state: Hokkaido
Study officials:
affiliation: Hokkaido University Hospital
name: Yoshito Komatsu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Komatsu Y, Yuki S, Sogabe S, Fukushima H, Nakatsumi H, Kobayashi Y, Iwanaga I, Nakamura M, Hatanaka K, Miyagishima T, Kudo M, Munakata M, Meguro T, Tateyama M, Sakata Y. Phase II study of combined chemotherapy with irinotecan and S-1 (IRIS) plus bevacizumab in patients with inoperable recurrent or advanced colorectal cancer. Acta Oncol. 2012 Sep;51(7):867-72. doi: 10.3109/0284186X.2012.682629. Epub 2012 May 4.