A Study of 2nd-line FOLFIRI ± Bevacizumab vs. Irinotecan ± Bevacizumab in mCRC

October 2, 2017 updated by: Ruihua Xu, Sun Yat-sen University

A Multinational, Randomized, Phase III Study of FOLFIRI With/Without Bevacizumab Versus Irinotecan With/Without Bevacizumab As Second-line Therapy in Patients With Metastatic Colorectal Cancer

The primary purpose of this study is to determine the non-inferiority of overall survival FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Primary endpoint: Overall survival (OS), Secondary endpoints: Progression-free survival (PFS), Time to treatment failure (TTF), Overall response rate (ORR),Disease Control Rate (DCR), Safety.

Study Type

Interventional

Enrollment (Anticipated)

280

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Cancer center of Sun Yat-sen University
        • Contact:
        • Sub-Investigator:
          • De-shen Wang, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
  2. Age ≥18 years at the time of informed consent
  3. ECOG performance status (PS) of 0-2
  4. Written informed consent prior to study-specific screening procedures
  5. Life expectancy of at least 90 days
  6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.
  7. Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL

Exclusion Criteria:

  1. History of other malignancy with a disease-free interval <5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
  2. With massive pleural effusion or ascites requiring intervention
  3. Radiological evidence of brain tumor or brain metastases
  4. Active infection including hepatitis

  5. Any of the following complication:

    i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)

  6. Any of the following medical history:

    Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency

  7. Previous treatment with irinotecan hydrochloride
  8. Current treatment with atazanavir sulfate
  9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
  10. Pregnant or lactating females, and males and females unwilling to use contraception
  11. Requires continuous treatment with systemic steroids
  12. Psychiatric disability that would preclude study compliance
  13. Otherwise determined by the investigator to be unsuitable for participation in the study
  14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
  15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
  16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
  17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
  18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease
  19. Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)
  20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
  21. Uncontrolled hypertension
  22. Urine dipstick for proteinuria >+2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: FOLFIRI +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
Biological: Bevacizumab
5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.
Other Names:
  • Avastin
Drug: 5-FU Bolus
400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.
Other Names:
  • fluorouracil
Drug: 5-FU Infusion
2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.
Other Names:
  • fluorouracil
Drug: l-LV (dl-LV)
200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.
Other Names:
  • Leucovorin
Drug: CPT-11
180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle
Other Names:
  • Irinotecan
EXPERIMENTAL: CPT-11 +/- Bevacizumab
Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1
Biological: Bevacizumab
5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.
Other Names:
  • Avastin
Drug: CPT-11
180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle
Other Names:
  • Irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Assessed until 1.5 years after the last patient enrolment
Time from the date of enrollment to death from any cause
Assessed until 1.5 years after the last patient enrolment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Assessed until 1.5 years after the last patient enrolment
Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
Assessed until 1.5 years after the last patient enrolment
Time to treatment failure (TTF)
Time Frame: Assessed until 1.5 years after the last patient enrolment
Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment.
Assessed until 1.5 years after the last patient enrolment
Overall Response Rate (ORR)
Time Frame: Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician.
Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
Disease Control Rate (DCR)
Time Frame: Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
Proportion of best overall response of CR, PR, or SD assessed by the attending physician.
Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
Incidence of Adverse Events (Adverse Reactions)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 14, 2011

Primary Completion (ANTICIPATED)

December 31, 2017

Study Completion (ANTICIPATED)

December 31, 2018

Study Registration Dates

First Submitted

September 23, 2017

First Submitted That Met QC Criteria

October 2, 2017

First Posted (ACTUAL)

October 6, 2017

Study Record Updates

Last Update Posted (ACTUAL)

October 6, 2017

Last Update Submitted That Met QC Criteria

October 2, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RECHANGE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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