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A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT01695772
Recruitment Status : Completed
First Posted : September 28, 2012
Results First Posted : July 28, 2016
Last Update Posted : June 9, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 27, 2012
First Posted Date  ICMJE September 28, 2012
Results First Submitted Date  ICMJE June 17, 2016
Results First Posted Date  ICMJE July 28, 2016
Last Update Posted Date June 9, 2017
Actual Study Start Date  ICMJE October 16, 2012
Actual Primary Completion Date April 4, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
Percentage of Participants Achieving Complete Resection (R0 Resection) [ Time Frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) ]
R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2012)
Complete resection rate (R0) in metastatic colorectal cancer patients with previously unresectable liver-only metastases [ Time Frame: approximately 3 years ]
Change History Complete list of historical versions of study NCT01695772 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
  • Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection) [ Time Frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) ]
    R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
  • Percentage of Participants Achieving Objective Response [ Time Frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) ]
    Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
  • Number of Participants With Disease Progression or Relapse or Death [ Time Frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) ]
    According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.
  • Progression Free Survival (PFS) [ Time Frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) ]
    Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.
  • Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18 [ Time Frame: Months 3, 6, 9, 12, 15, and 18 ]
    Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.
  • Number of Participants With Disease Relapse or Death [ Time Frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) ]
  • Disease Free Survival (DFS) [ Time Frame: Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years) ]
    Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.
  • Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12 [ Time Frame: Months 3, 6, 9, and 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2012)
  • Objective response rate (ORR), tumor assessments according to RECIST v.1.1 criteria [ Time Frame: approximately 3 years ]
  • Progression-free survival (PFS) for all patients enrolled in the study [ Time Frame: approximately 3 years ]
  • Disease-free survival (DFS) for patients who achieve complete resection [ Time Frame: approximately 3 years ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
Official Title  ICMJE A Multi-Center, Single-Arm, Pilot Study of 5-FU Based Doublet Chemotherapy Plus Bevacizumab as Neoadjuvant Therapy for Patients With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
Brief Summary This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: 5-FU based doublet chemotherapy
    Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.
  • Drug: bevacizumab
    5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively
    Other Name: Avastin
Study Arms  ICMJE Experimental: Bevacizumab
Interventions:
  • Drug: 5-FU based doublet chemotherapy
  • Drug: bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2012)
50
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 12, 2016
Actual Primary Completion Date April 4, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult Chinese participants, 18-75 years of age
  • Histologically confirmed adenocarcinoma in colon or rectum with primary lesion surgically removed
  • Previously untreated unresectable liver-only metastases
  • Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting of experienced hepatic surgeons, medical oncologist and radiologist).
  • No previous treatment against liver metastases, including chemotherapy, surgery, radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy
  • Adequate hematological, renal and hepatic function
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Life expectancy greater than (>) 3 months

Exclusion Criteria:

  • The relapse has occurred within 6 months of completion of the adjuvant treatment
  • Expected impossible to achieve complete resection (R0 resection) and/or gain 30% residual liver volume even with responsive neoadjuvant therapy
  • Participant cannot tolerate the surgery
  • Other malignancies in the past 5 years, except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
  • Any extrahepatic metastases and/or recurrence of the primary tumor
  • Any residual toxicity from previous chemotherapy (except alopecia) of National Cancer Institute Common Toxicity Criteria (NCI CTC) v.4.0 grade 2
  • Hypertension crisis or encephalopathy
  • Pregnant or lactating women
  • Clinically significant cardiovascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Current or recent (within 10 days of study drug initiation) use of full dose of aspirin, clopidrogel or warfarin
  • History or evidence of Central Nervous System (CNS) disease (for example, primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01695772
Other Study ID Numbers  ICMJE ML28419
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP