Bevacizumab Plus Capecitabin vs S-1 as Maintenance Treatment Following First-line Chemotherapy in the Patients With Advanced Colorectal Adenocarcinoma

Bevacizumab Plus Capecitabin vs S-1 as Maintenance Treatment Following First-line Chemotherapy in the Patients With Advanced Colorectal Adenocarcinoma. A Phase 3 Randomised Controlled Trial

Bevacizumab plus capecitabin is a standard maintenance treatment following first-line chemotherapy in the patients with advanced colorectal adenocarcinoma. However, hand-foot syndrome induced by capecitabin will bother the patient to decrease the quality of life. S-1, an alternative of fluoropyrimidine, was proved non-inferior efficacy with lower hand-foot syndrome as first-line chemotherapy in advanced colorectal adenocarcinoma in the studies. The investigators are going to test the efficacy and safety of bevacizumab plus S-1 as maintenance treatment compared with bevacizumab plus capecitabin in colorectal adenocarcinoma

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: S-1; Drug: Bevacizumab; Drug: Capecitabine

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Rongbo Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Criteria

Before the start of induction therapy:

Inclusion Criteria:

Histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained); Distant metastases (patients with only local recurrence are not eligible); Unidimensionally measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation; In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.

Ongoing or planned first line treatment with 6 cycles of Xeloda, Eloxatin, and Avastin.

Exclusion criteria Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment Any prior adjuvant treatment after resection of distant metastases Previous systemic treatment for advanced disease

At randomisation:

Inclusion criteria:

WHO performance status 0-1 (Karnofsky PS > 70%); Disease evaluation with proven SD, PR or CR according to RECIST after 6 cycles of MTD chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and randomisation performed in week 3-5 of the 6th cycle (see time table); Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb > 6.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases); Life expectancy > 12 weeks; Age >= 18 yrs; Negative pregnancy test in women with childbearing potential; Expected adequacy of follow-up; Institutional Review Board approval; Written informed consent Exclusion criteria History or clinical signs/symptoms of CNS metastases; History of a second malignancy ≤ 5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin; Previous intolerance of XelodaR, EloxatinR, and/or AvastinR for which any of these drugs have been permanently discontinued; patients with previous dose reductions or delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are eligible, and retreatment with EloxatinR after PFS1 should depend on the grade of neurotoxicity at that moment; Known dihydropyrimidine dehydrogenase (DPD) deficiency; (Planned) radical resection of all metastatic disease; Uncontrolled hypertension, i.e. consistently > 150/100 mmHg; Use of more than 3 antihypertensive drugs; Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism); Any of these significant cardiovascular events during previous fluoropyrimidine therapy; Chronic active infection; Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs; Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as >CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets); Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if started during induction therapy); Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bevacizumab plus s-1	Drug: S-1; S-1 is administered orally on days 1 to 14 of a 21-day cycle. Patients are assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA <1.25m2), 50 mg (BSA >1.25 to <1.50 m2), or 60 mg (BSA >1.50 m2).
Active Comparator: bevacizumab plus capecitabin	Drug: Bevacizumab; Bevacizumab (7.5 mg/kg) is administered by intravenous infusion over the course of 30 to 90 min on day 1 of each 3-week cycle.; Drug: Capecitabine; Capecitabine 2000mg/m2/d is administered orally on days 1 to 14 of a 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	The length of time from enrollment until the time of progression of disease	From enrollment to progression of disease. Estimated about 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The length of time from enrollment until the time of death	From enrollment to death of patients. Estimated about 1 year.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	According to NCI CTCAE 4.03 criteria	From enrollment to 3 months after treatment

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: October 13, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: bevacizumab; maintenance; s-1; capecitabin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Bevacizumab
• Other Study ID Numbers: FNF 012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No