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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01695772
First received: September 27, 2012
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
This open-label, single arm, multicenter study will evaluate 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 will 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 experience progressive disease or unacceptable toxicity.

Condition Intervention Phase
Colorectal Cancer
Drug: 5-FU based doublet chemotherapy
Drug: bevacizumab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 04 April 2015 (up to approximately 2.5 years overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Disease Progression or Relapse or Death [ Time Frame: Screening until disease progression or death until data cutoff on 04 April 2015 (up to approximately 2.5 years overall) ] [ Designated as safety issue: No ]
    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 04 April 2015 (up to approximately 2.5 years overall) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Disease Relapse or Death [ Time Frame: Screening until disease progression or death until data cutoff on 04 April 2015 (up to approximately 2.5 years overall) ] [ Designated as safety issue: No ]
  • Disease Free Survival (DFS) [ Time Frame: Complete resection date up to disease relapse or death until data cutoff on 04 April 2015 (up to approximately 2.5 years) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: October 2012
Study Completion Date: April 2016
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab 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 will be as per standard of practice and the dosage of 5-FU based doublet chemotherapy will be as per product labels.
Drug: bevacizumab
5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively
Other Name: Avastin

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01695772

Locations
China
Beijing, China, 100142
Guangzhou, China, 510060
Hangzhou, China, 310009
Harbin, China, 150001
Shanghai, China, 200032
Shenyang, China, 110042
Wuhan, China, 430022
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01695772     History of Changes
Other Study ID Numbers: ML28419 
Study First Received: September 27, 2012
Results First Received: June 17, 2016
Last Updated: June 17, 2016
Health Authority: China: State Food and Drug Administration (SFDA)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 25, 2016