Clinical trial NCT03380689: Phase I Study of Biweekly SIRB Regimen for Metastatic Colorectal Cancer
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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Fujian Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2017-12-21
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum tolerance dose
timeFrame: From enrollment to completion of study. Estimated about 12 months.
Secondary outcomes:
measure: Dose limiting toxicity
timeFrame: From enrollment to completion of study. Estimated about 12 months.
measure: Objective response rate
timeFrame: From enrollment to 6 months after treatment.
measure: Progression-free survival
timeFrame: From enrollment to progression of disease. Estimated about 6 months.
measure: Overall survival
timeFrame: From enrollment to death of patients. Estimated about 1 year.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Rongbo Lin
state: Fujian
Study officials:
affiliation: Fujian Cancer Hospital
name: Rongbo Lin, MD
role: STUDY_CHAIR
References: