Phase I Study of Biweekly SIRB Regimen for Metastatic Colorectal Cancer (SIRB2)

Phase I Study of Combination Therapy With S-1, Irinotecan, and Bevacizumab as 1-line Chemotherapy in Patients With Advanced Colorectal Cancer.

Phase I Study of biweekly combination therapy with S-1, Irinotecan, and Bevacizumab as 1-line Chemotherapy in Patients With Advanced Colorectal Cancer.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: S-1; Drug: Irinotecan; Drug: Bevacizumab

Detailed Description

In several clinical studies from Japan and South Korea, the combination regimen of S-1 and irinotecan has shown efficacy in the treatment of advanced colorectal cancer, and a Phase III study（TRICOLORE） showed that the combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) is not inferior to the oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Here, we design this phase I study to explore the Chinese population's tolerability and efficacy of Biweekly SIRB Regimen(S-1/irinotecan/bevacizumab) and to explore the recommended dose of irinotecan in this regimen.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Rongbo Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed colorectal carcinoma with inoperable, locally advanced, or metastatic disease, not amenable to curative therapy
• Measurable disease or non-measurable but assessable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
• 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.
• Age ≥20 years
• Life expectancy of at least 3 months
• ECOG PS of 0 or 1

• Adequate function of major organs as defined below:

  • Hemoglobin ≥9.0g/dL
  • White blood cell count ≥3,500/mm3
  • Neutrophil count ≥1,500/mm3
  • Platelet count ≥100,000/mm3
  • AST and ALT ≤100 U/L (<200 U/L in patients with liver metastasis)

  • Serum creatinine ≤1.2 mg/dL

    • Creatinine clearance estimate by the Cockcroft-Gault method >50 mL/min (reduce initial dosage by one step if ≥50 but <80 mL/min)
• Able to take capsules orally.
• No electrocardiographic abnormalities within 28 days before enrollment that would clinically preclude the execution of the study, as judged by the investigator.
• Voluntary written informed consent.

Exclusion Criteria:

• Serious drug hypersensitivity or a history of drug allergy
• Active double cancer
• Active infections (e.g., patients with pyrexia of 38℃ or higher)
• History of gastrointestinal perforation, intestinal tract paralysis, or ileus within 1 year.
• Uncontrolled hypertension
• Serious complications (e.g., pulmonary fibrosis, interstitial pneumonitis, heart failure, renal failure, hepatic failure, or poorly controlled diabetes)
• Moderate or severe ascites or pleural effusion requiring treatment
• Watery diarrhea
• Treatment with flucytosine or atazanavir sulfate
• Metastasis to the CNS
• Pregnant women, possibly pregnant women, women wishing to become pregnant, and nursing mothers. Men who are currently attempting to conceive children.
• Severe mental disorder
• Continuous treatment with steroids
• Urine dipstick for proteinuria should be <2+
• Patient with a past history of thrombosis, cerebral infarction, myocardial infarction, or pulmonary embolism
• Major surgical procedure, open biopsy, or clinically significant traumatic injury within 4 weeks
• Long-term daily treatment with aspirin (>325 mg/day)
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
• 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: SIRB2; Biweekly combination therapy with S-1, Irinotecan, and Bevacizumab

Drug: S-1; - S-1 is administered orally on days 1 to 7 of a 14-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).; Other Names: S1; Drug: Irinotecan; - CPT-11 was administrated as a 90-min intravenous infusion on day 1 of a 14-day cycle. Five escalating dose levels of CPT-11 were prepared, at an initial dose of 75mg/m2/day (level 1), stepping up to 100 (level 2), 125 (level 3), 150 (level 4) or 175 (level 5) mg/m2/day.; Other Names: CPT-11; Drug: Bevacizumab; - Bevacizumab (5 mg/kg) is administered by intravenous infusion over the course of 30 to 90 min on day 1 of each 2-week cycle.; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerance dose	Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.	From enrollment to completion of study. Estimated about 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity	Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria.	From enrollment to completion of study. Estimated about 12 months.
Objective response rate	Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).	From enrollment to 6 months after treatment.
Progression-free survival	The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).	From enrollment to progression of disease. Estimated about 6 months.
Overall survival	The length of time from enrollment until the time of death (OS, overall survival).	From enrollment to death of patients. Estimated about 1 year.

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 5, 2018
• Primary Completion (ANTICIPATED): July 5, 2018
• Study Completion (ANTICIPATED): January 5, 2019

Study Registration Dates

• First Submitted: December 17, 2017
• First Submitted That Met QC Criteria: December 17, 2017
• First Posted (ACTUAL): December 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: December 1, 2017

More Information

Terms related to this study

• 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: FNF008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No