Chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases The CHARISMA randomized multicenter clinical trial

• Register: EUCTR
• Last refreshed on: 13 May 2024
• Main ID: EUCTR2013-004952-39-NL
• Date of registration: 23/07/2014
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC Cancer Institute
• Public title: Chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases The CHARISMA randomized multicenter clinical trial
• Scientific title: Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases The CHARISMA randomized multicenter clinical trial - CHARISMA
• Date of first enrolment: 29/07/2014
• Target sample size: 224
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004952-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Trial Bureau
• Affiliation: Erasmus MC Cander Institute

• Name: Trial Bureau
• Affiliation: Erasmus MC Cander Institute

Key inclusion & exclusion criteria

Inclusion criteria:
• Age = 18 years.
• ECOG performance status 0 or 1.
• Histologically confirmed primary colorectal carcinoma. Primary colorectal carcinomas to be included are:
1. Previously resected histologically proven colorectal carcinoma
2. Coloncarcinoma still in situ, deemed suitable for resection at the time of liver surgery
3. Rectal carcinoma still in situ, requiring no neo-adjuvant radiotherapy, deemed suitable for resection at the time of liver surgery
4. Rectal carcinoma still in situ, requiring short-course neo-adjuvant radiotherapy, deemed suitable for resection at the time of liver surgery
• Radiologically confirmed and resectable liver metastasis of colorectal cancer after surgery.
• Clinical risk score of 3-5 (Fong et al.).
• Adequate bone marrow, liver and renal function as assessed by laboratory requirements to be conducted within 15 days prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 179

Exclusion criteria:
• Prior adjuvant chemotherapy for the primary colorectal carcinoma given <6 months prior to detection of the liver metastases.
• Prior non colorectal malignancies, except for patients with basal or squamous cell carcinoma of the skin, or patients with carcinoma in situ of the cervix.
• Presence of extrahepatic disease
• Locally advanced rectal cancer in situ requiring long-course pre-operative chemoradiotherapy
• Major surgical procedure < 4 weeks prior to randomization.
• Females with a positive pregnancy test (within 14 days before treatment start).
• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake.
• Clinically significant (i.e. active) cardiovascular disease e.g. cerebrovascular accidents (= 6 months prior to randomization), myocardial infarction (= 1 year prior to randomization), uncontrolled hypertension while receiving chronic medication, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhytmia requiring medication.
• Serious, non-healing wound, ulcer, or bone fracture.
• Serious intercurrent infections (uncontrolled or requiring treatment).
• Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Colorectal liver metastases

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Oxaliplatin
Product Name: Oxaliplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 130-

Trade Name: Xeloda / Capecitabine
Product Name: Xeloda/Capecitabine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Capecitabine/Xeloda
Other descriptive name: CAPECITABINE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Primary end point(s): Primary endpoint of the study will be overall survival (OS), calculated from the date of randomization to the date of death from any cause of the patient. Patients still alive at the date of last contact will be censored.

Main Objective: The primary objective of the study is to compare the efficacy, as assessed by overall survival (OS), of surgery and neo-adjuvant chemotherapy to surgery alone in patients with liver metastases of colorectal cancer and a high clinical risk score.

Secondary Objective: • To compare progression free survival (PFS) between the 2 arms
• To determine quality of life in the two study arms
• To determine treatment response on neoadjuvant chemotherapy
• To compare morbidity of surgery and resection rate between the 2 arms
• To evaluate whether CEA can predict for treatment response, PFS and OS

Timepoint(s) of evaluation of this end point: After 126 events.

Secondary Outcome(s)

Secondary end point(s): Progression free survival (PFS) will be defined from the date of randomization to the first event defined as local/distant recurrence or progression or death from any cause.

Timepoint(s) of evaluation of this end point: After 126 events.

Secondary ID(s)

CHARISMA

Source(s) of Monetary Support

KWF Kankerfonds

Ethics review

Status: Approved
Approval date: 29/07/2014
Contact: