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Biomarkers for Apatinib and Bevacizumab in Second-line Therapy for Colorectal Cancer(BABST-C) (BABST-C)

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ClinicalTrials.gov Identifier: NCT03743428
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
Wan He, Shenzhen People's Hospital

Tracking Information
First Submitted Date  ICMJE November 4, 2018
First Posted Date  ICMJE November 16, 2018
Last Update Posted Date September 24, 2019
Estimated Study Start Date  ICMJE October 22, 2019
Estimated Primary Completion Date November 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Identify biomarkers specific to apatinib or bevacizumab by transcriptome analysis [ Time Frame: 4 years ]
    Identify differentially expressed genes specific to apatinib or bevacizumab by the next‐generation RNA‐seq technology .
  • Identify biomarkers specific to apatinib or bevacizumab by proteomic analysis [ Time Frame: 4 years ]
    Identify proteomic molecules specific to apatinib or bevacizumab by the photoreactive crosslinking, pull-down, affinity purification and mass spectrometry (AP-MS) analyses
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Progression-free Survival (PFS) [ Time Frame: The follow-up period ranges from the first patient recruited to the last patient within 6 months after admission, up to 2 years ]
    PFS was defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) [according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1] or death due to any cause, whichever was first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment.
  • Overall Survival (OS) [ Time Frame: The follow-up period ranges from the first patient recruited to the last patient within 6 months after admission,up to 2 years ]
    OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Biomarkers for Apatinib and Bevacizumab in Second-line Therapy for Colorectal Cancer(BABST-C)
Official Title  ICMJE The Biomarkers Identification for Apatinib and Bevacizumab in the Second-line Therapy for Colorectal Cancer: A Randomised Controlled Trial
Brief Summary Bevacizumab, an antibody against vascular endothelial generated factor (VEGF), combined with the fluorouracil-based chemotherapy regimens has been approved in the 1st and 2nd line treatments for metastatic colorectal cancers(mCRC). Other inhibitors of the VEGF pathway, such as Ramucirumab and Aflibercept are also approved in the 2nd line therapy. Apatinib is a small molecule tyrosine kinase inhibitor (TKI), which can highly selectively bind to and strongly block VEGF receptor 2 (VEGFR - 2), resulting in reduced cell migration, proliferation, and tumor microvascular density mediated by VEGF . In this study, the patients who have progressed following or on the first-line oxaliplatin and fluorouracil(5-FU) combined with bevacizumab are randomised into two arms(FOLFIRI plus apatinib or FOLFIRI plus bevacizumab) in the 2nd line setting. To identify specific biomarkers at the genetic and proteomic levels between two arms is the primary end point.
Detailed Description

Based on inclusion and exclusion criteria, eligible mCRC patients are enrolled. the chest-abdonimal-pelvic CT with brain MRI and blood tests are examined to assess base-line measurable lesions and guarantee adequate organ function prior to enrollment. The written consents are signed before enrollment. Randomise patients into two arms: Arm A-apatinib plus FOLFIRI regimen and arm B-bevacizumab plus FOLFIRI regimen. Patients will be given full-dose drugs or reduced-dose drugs if serious toxicities ( CTCAE v4.0 criteria grade 3/4) are complained since previous cycle of treatment.

Symptoms and blood test results (including carcinoembryonic antigen(CEA)and CA199) before each cycle will be recorded. Radiological assessment consisting of chest-abdonimal-pelvic CT together with brain MRI will be performed every 3 months.

Collect biopsy specimens and peripheral blood from mCRC patients every 3 months since randomisation. Identify differential biomarkers between apatinib and bevacizumab and define these biomarkers' prognostic and predictive significances.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Head-to-head comparison of apatinib versus bevacizumab plus second-line chemotherapy regimen FOLFIRI for treatment of metastatic colorectal cancer
Masking: None (Open Label)
Masking Description:
No masking
Primary Purpose: Basic Science
Condition  ICMJE Colorectal Neoplasms
Intervention  ICMJE
  • Drug: Apatinib Mesylate Tablets
    Apatinib combinated with FOLFIRI regimen as the second-line chemotherapy for mCRC
    Other Name: YN968D1
  • Drug: Bevacizumab Injection
    Bevacizumab combinated with FOLFIRI regimen as the second-line chemotherapy for mCRC
    Other Name: Avastin
Study Arms  ICMJE
  • Experimental: Apatinib-FOLFIRI
    Apatinib Mesylate Tablets 250mg po qd Irinotecan 180 mg/m2 IV over 30-90 minutes,day 1 Leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion,day 1 5-FU 400 mg/m2 IV bolus day 1,then 1200 mg/m2/d x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion Repeat every 2 weeks.
    Intervention: Drug: Apatinib Mesylate Tablets
  • Active Comparator: Bevacizumab-FOLFIRI
    Bevacizumab Injection 5mg/kg IV,day 1 Irinotecan 180 mg/m2 IV over 30-90 minutes,day 1 Leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion,day 1 5-FU 400 mg/m2 IV bolus day 1,then 1200 mg/m2/d x 2days (total 2400 mg/m2 over 46-48 hours) continuous infusion Repeat every 2 weeks.
    Intervention: Drug: Bevacizumab Injection
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 13, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date November 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer confirmed by histology
  • Age ≥18 years ≤ 70 years at the time of informed consent
  • Eastern Cooperative Oncology Group(ECOG)performance status (PS) ≤ 1
  • Provided informed consent before study-specific screening procedures
  • Life expectancy not less than 90 days
  • Participants have progressive disease on or within 6 months post the combination of bevacizumab and 5-FU/leucovorin+oxaliplatin(FOLFOX) or capecitabine+oxaliplatin(CAPOX) as the first-line chemotherapy for metastatic colorectal cancer
  • Adequate organ function based on the following laboratory values obtained within 14 days prior to 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, aspartate aminotransferase (AST), alanine aminotransferase (ALT): ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
  • Adequate blood coagulation function [International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be in a stable phase of anticoagulant therapy and if taking oral anticoagulation, participants must have an INR ≤3 without clinically significant active bleeding or a high risk of bleeding
  • A historical colorectal cancer tissue sample is available for assessment of biomarkers with signed consent
  • Signed informed consent to be provided

Exclusion Criteria:

  • History of other malignancy with a disease-free survival <5 years (excluding curatively treated cutaneous basal cell carcinoma, curatively treated cervical in situ carcinoma , and gastroenterological carcinoma confirmed to be cured by endoscopic mucosal resection)
  • With a large amount of pleural effusions or ascites requiring intervention
  • Radiological evidence of brain metastases or brain tumor
  • Actively infectious condition including hepatitis
  • One of the following complications: 1) Gastrointestinal obstruction (including paralytic ileus) or gastrointestinal bleeding 2) Symptomatic cardiac disease (including unstable angina, myocardial infarction, and heart failure) 3) Pulmonary fibrosis or interstitial pneumonia 4) Uncontrolled diarrhea (that affects daily activities although adequate therapy 5) Uncontrolled diabetes mellitus
  • One of the following medical histories: 1) Myocardial infarction: One episode within one year prior to enrollment or two or more lifetime episodes 2) Remarkable hypersensitivity to any of the study drugs ii) History of side effect to fluoropyrimidines suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency
  • Pregnant or lactating females, and males and females reluctant to use contraception
  • Psychiatric disability that would disturb study compliance
  • Other conditions determined by the investigator to be not suitable for participation in the study
  • History of concurrent gastrointestinal perforation or gastrointestinal perforation within 1 year prior to enrollment
  • Pulmonary hemorrhage/hemoptysis ≥ Grade 2 (identified as bright red blood of not less 2.5mL) within 1 month before enrollment.
  • History of thoracotomy,laparotomy, or intestinal resection within 28 day prior to enrollment
  • Unhealed wound (other than suture wounds due to implantation of a central venous port), traumatic fracture, or gastrointestinal ulcer
  • Current cerebrovascular disease or thromboembolism or either within 1 year before enrollment
  • Current anticoagulation therapy or requiring anticoagulation agents (> 325 mg/day of aspirin)
  • Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR

    ≥1.5 within 14 days before enrollment)- Page 6 of 7 [DRAFT] -

  • Uncontrolled hypertension Urine dipstick for proteinuria >+2
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: Wan He, PhD,MD +8675522942449 hewanshenzhen@hotmail.com
Contact: Ruilian Xu, MD +8675522942497 xuruilian@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03743428
Other Study ID Numbers  ICMJE Shenzhen CRC-003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Wan He, Shenzhen People's Hospital
Study Sponsor  ICMJE Shenzhen People's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wan He, PhD,MD Shenzhen People's Hospital
PRS Account Shenzhen People's Hospital
Verification Date September 2019

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