The Effects of RFA in Combination With Second-line Chemotherapy and Bevacizumab on Unresectable CRLM

NCT03686254 | Unknown Phase 2

• 1 other identifier: LC2016ZD014
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Basing on the strong evidence from former researches, patients with CRLM can benefit from the treatment of bevacizumab combined with sencond-line chemotherapy. Recently, although with the popularization of RFA, the role that RFA plays in the long term survival of patients with metastatic colorectal cancer (CRC) is still confused. In this designed, randomized, controlled, prospective, and open clinical trial, the effectiveness of RFA combined with second-line chemotherapy + bevacizumab on unresectable CRLM is going to be evaluated compared with that of second-line chemotherapy + bevacizumab. After screened by inclusion and exclusion criteria, the eligible subjects will be randomly allocated into the experimental group-with the treatment of RFA + second-line chemotherapy + bevacizumab and control group-with the treatment of second-line chemotherapy + bevacizumab equally.

Conditions

Colorectal Neoplasms Malignant

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS), Month

  From the date of randomization until the date of death due to any cause, assessed up to 36 months

Secondary Outcomes (2)

• Progress free survival (PFS), Month

  From the date of randomization until the date of first documented tumor progression or date of death before progression due to any cause, assessed up to 36 months

• Time to progression (TTP), Month

  From the date of randomization until the date of first documented tumor progression, assessed up to 36 months

Study Arms (2)

The control Arm

ACTIVE COMPARATOR

bevacizumab and second-line chemotherapy

Drug: Bevacizumab and second-line chemotherapy

The experimental Arm

EXPERIMENTAL

RFA, bevacizumab and second-line chemotherapy

Combination Product: RFA, bevacizumab and second-line chemotherapy

Interventions

RFA, bevacizumab and second-line chemotherapy COMBINATION_PRODUCT

Navigated by CT-ultrasound merged images, RFA is taken in the experimental arm at the first day of the first cycle during the second-line therapy. Bevacizumab is given to patients in all arms every 2 weeks (5mg/kg) or 3 weeks (7.5mg/kg), intravenous drip(VD). The second-line chemotherapies include FOLFIRI \[Irinotecan 180 mg/m2 D1+Calcium folinatc 400 mg/m2 or Calcium Levofolinate 200 mg/m2 D1+5-FU 400 mg/m2 D1, 2400 mg/m2 D1-2(46-48h), q2W\] or irinotecan monotherapy (125 mg/m2 D1, 8, q3W or 180 mg/m2 D1, q2W), mFOLFOX6 \[Oxaliplatin 85 mg/m2 D1+Calcium folinatc 400 mg/m2 or Calcium Levofolinate 200 mg/m2 D1+5-FU 400 mg/m2 D1, 2400 mg/m2 D1-2(46-48h), q2W\] or CapeOX (Oxaliplatin 130 mg/m2 D1+Capecitabine 1000 mg/m2 Bid D1-14, q3W)，or irinotecan+oxaliplatin (Oxaliplatin 85 mg/m2 D1+Irinotecan 200 mg/m2 D1, q3W). Among these strategies, the treatment cycle of FOLFIRI, irinotecan monotherapy and mFOLFOX6 is two weeks, while three weeks in CapeOX and irinotecan + oxaliplatin.

The experimental Arm

Bevacizumab and second-line chemotherapy DRUG

Bevacizumab is given to patients in all arms every 2 weeks (5mg/kg) or 3 weeks (7.5mg/kg), intravenous drip(VD). The second-line chemotherapies include FOLFIRI \[Irinotecan 180 mg/m2 D1+Calcium folinatc 400 mg/m2 or Calcium Levofolinate 200 mg/m2 D1+5-FU 400 mg/m2 D1, 2400 mg/m2 D1-2(46-48h), q2W\] or irinotecan monotherapy (125 mg/m2 D1, 8, q3W or 180 mg/m2 D1, q2W), mFOLFOX6 \[Oxaliplatin 85 mg/m2 D1+Calcium folinatc 400 mg/m2 or Calcium Levofolinate 200 mg/m2 D1+5-FU 400 mg/m2 D1, 2400 mg/m2 D1-2(46-48h), q2W\] or CapeOX (Oxaliplatin 130 mg/m2 D1+Capecitabine 1000 mg/m2 Bid D1-14, q3W)，or irinotecan+oxaliplatin (Oxaliplatin 85 mg/m2 D1+Irinotecan 200 mg/m2 D1, q3W). Among these strategies, the treatment cycle of FOLFIRI, irinotecan monotherapy and mFOLFOX6 is two weeks, while three weeks in CapeOX and irinotecan + oxaliplatin.

The control Arm

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• CRLM patients with histopathological diagnosis. 2.Tumor progression after first-line therapy or intolerable adverse events occur;
• The first-line therapy should be the standard regimen recommended by NCCN guideline.
• Tumor progression indicates: progression occurs during the process or within three months after the final treatment of first-line therapy; progression occurs during the period of adjunctive therapy/neoadjuvant therapy or within six months after adjunctive therapy finished.
• Prior treatment with bevacizumab or cetuximab is allowed. 3.Aged between 16-80 years old (16 and 80 years old are included), with no limitation of gender; 4.ECOG scores 0-1; 5.At least one measurable liver metastasis according to RECIST 1.1 criteria; 6.The liver metastasis is no larger than 50% of total liver lesions; 7.Determined as unresectable liver metastasis by the multidisciplinary team consisting of liver surgeons and medical oncologists;
• )R0 resection cannot be operated on liver metastases. 2)Hepatic artery or the branches of portal vein is invaded. 3)The three main hepatic veins are surrounded by liver metastases. 4)Extrahepatic metastases coexist. 8.Life expectancy is above three months; 9.With full appreciation, voluntary and a signed informed consent; 10.Vital organs with normal function:
• Routine blood test: hemoglobin (HGB) 85g/L, platelet (PLT) 80/L, and neutrophils 1.5/L;
• Normal coagulation function originally or after treatment (if exceeding reference level, whether it is still within normal range should be determined by researchers);
• Total bilirubin(BIL) is 1.5 times higher than the upper normal limit, alanine aminotransferase (ALT) and aspartic transaminase (AST) are 5 times higher than the upper normal limit;
• Urine protein ranges from - to +, and serum creatinine 1.5×ULN; 11.Negative pregnancy test results in women of childbearing age (7 days before RFA treatment), and effective contraceptive measures must be adopted until 6 m after the last treatment.

You may not qualify if:

• Prior treatment with other clinically experimental drugs, systemic chemotherapy, immunotherapy or targeted therapy within 2 weeks before this trial;
• Prior treatment on liver metastases with radiotherapy, hepatic arterial infusion chemotherapy, transcatheter hepatic arterial chemoembolization, cryoablation, microwave ablation or RFA within 2 weeks before this trial;
• Abnormal coagulation function and with hemorrhagic tendency;
• Damaged or infectious skin in the puncture or electrode sticking area;
• Complicated by active hepatitis or hepatic failure;
• Complicated by severe hypertension or hypertensive crisis (systolic pressure 180 mmHg and/or diastolic pressure 110 mmHg in a resting state);
• Impaired cardiac function, manifested as left ventricular ejection fraction 50%, severe arrhythmia, unstable angina, history of myocardial infarction within 1 year before this trial, or congestive heart-failure in NYHA class III or IV;
• History of stroke within 6 months;
• History of other malignancies except for colorectal cancer within 5 years;
• Abnormal medical or psychologic status that may hamper the ongoing trial or signing an informed consent;
• No or limited legal capacity;
• Pregnant or breast-feeding women;
• Combined acute infection or human immunodeficiency virus (HIV) infection;
• With contradictions for bevacizumab; 1)History of severe hemorrhage or hemoptysis 1 month before this trial 2)Urine protein 2+, and 24-hour urinary protein quantitative 2g 3)Allergy to bevacizumab or any active ingredients 4)Patients with surgery, major trauma or fracture within 4 weeks 5)Unhealed wounds, intestinal stomas or peptic ulcer
• Treated with other experimental antineoplastic drugs.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (3)

• Hur H, Ko YT, Min BS, Kim KS, Choi JS, Sohn SK, Cho CH, Ko HK, Lee JT, Kim NK. Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases. Am J Surg. 2009 Jun;197(6):728-36. doi: 10.1016/j.amjsurg.2008.04.013. Epub 2008 Sep 11.

  PMID: 18789428 BACKGROUND

• Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB 3rd; Eastern Cooperative Oncology Group Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007 Apr 20;25(12):1539-44. doi: 10.1200/JCO.2006.09.6305.

  PMID: 17442997 BACKGROUND

• Ruers T, Van Coevorden F, Punt CJ, Pierie JE, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Folprecht G, Van Cutsem E, Ducreux M, Nordlinger B; European Organisation for Research and Treatment of Cancer (EORTC); Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Inst. 2017 Sep 1;109(9):djx015. doi: 10.1093/jnci/djx015.

  PMID: 28376151 RESULT

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Radiofrequency Ablation; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Wangjun Liao

  Nanfang Hospital, Southern Medical University

  STUDY CHAIR

Central Study Contacts

Wangjun Liao

CONTACT

62787731; nfyyliaowj@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Oncology Department

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: July 16, 2018
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: September 26, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)