Back to results

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

Primary Purpose

Metastatic Colorectal Cancer

Status

Withdrawn

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

S-1

Irinotecan

Bevacizumab

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Rongbo Lin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SIRB2

Arm Description

Biweekly combination therapy with S-1, Irinotecan, and Bevacizumab

Outcomes

Primary Outcome Measures

Maximum tolerance dose

Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.

Secondary Outcome Measures

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.

Objective response rate

Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).

Progression-free survival

The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).

Overall survival

The length of time from enrollment until the time of death (OS, overall survival).

Full Information

NCT ID

NCT03380689

First Posted

December 17, 2017

Last Updated

March 4, 2021

Sponsor

Fujian Cancer Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03380689

Brief Title

Phase I Study of Biweekly SIRB Regimen for Metastatic Colorectal Cancer

Acronym

SIRB2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Withdrawn

Why Stopped

There is no fund to support it

Study Start Date

January 5, 2018 (Anticipated)

Primary Completion Date

July 5, 2018 (Anticipated)

Study Completion Date

January 5, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fujian Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SIRB2

Arm Type

Experimental

Arm Description

Biweekly combination therapy with S-1, Irinotecan, and Bevacizumab

Intervention Type

Drug

Intervention Name(s)

S-1

Other Intervention Name(s)

Intervention Description

- 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).

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Other Intervention Name(s)

CPT-11

Intervention Description

- 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.

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

- 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.

Primary Outcome Measure Information:

Title

Maximum tolerance dose

Description

Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.

Time Frame

From enrollment to completion of study. Estimated about 12 months.

Secondary Outcome Measure Information:

Title

Dose limiting toxicity

Description

Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria.

Time Frame

From enrollment to completion of study. Estimated about 12 months.

Title

Objective response rate

Description

Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).

Time Frame

From enrollment to 6 months after treatment.

Title

Progression-free survival

Description

The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).

Time Frame

From enrollment to progression of disease. Estimated about 6 months.

Title

Overall survival

Description

The length of time from enrollment until the time of death (OS, overall survival).

Time Frame

From enrollment to death of patients. Estimated about 1 year.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rongbo Lin, MD

Organizational Affiliation

Fujian Cancer Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Rongbo Lin

City

Fuzhou

State/Province

Fujian

ZIP/Postal Code

350014

Country

China

12. IPD Sharing Statement

Learn more about this trial

Phase I Study of Biweekly SIRB Regimen for Metastatic Colorectal Cancer

We'll reach out to this number within 24 hrs