Phase II Trial of Combination Therapy With Irinotecan, S-1, and Bevacizumab (IRIS/Bev) in Patients With Unresectable or Recurrent Colorectal Cancer

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: S-1, Irinotecan, Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8038
      • Hokkaido University Hospital (Hokkaido Gastrointestinal Cancer Study Group)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; S-1, Irinotecan, Bevacizumab

Drug: S-1, Irinotecan, Bevacizumab; S-1 is administered orally on days 1 to 14 of a 28-day cycle. Patients are assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA <1.25m2), 50 mg (BSA >1.25 to <1.50 m2), or 60 mg (BSA >1.50 m2). Irinotecan 100 mg/m2 is administered by intravenous infusion on days 1 and 15. Bevacizumab 5 mg/kg (body weight)is administered by intravenous infusion on days 1 and 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety	any time

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival, Response rate, Overall survival, Treatment situation	every course for first three courses, then every other course

Collaborators and Investigators

• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yoshito Komatsu, Hokkaido University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 5, 2007
• First Submitted That Met QC Criteria: December 5, 2007
• First Posted (Estimate): December 7, 2007

Study Record Updates

• Last Update Posted (Estimate): November 2, 2012
• Last Update Submitted That Met QC Criteria: November 1, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Bevacizumab; S-1; Irinotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Bevacizumab; Irinotecan
• Other Study ID Numbers: 01023018