The primary objective is overall survival (OS).Secondary objectives are progression free survival (PFS), grade 3 and 4 chemotherapy related toxicity, surgery related morbidity and mortality (30 day and 90 day), quality of life (QoL), number of…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is overall survival in the intent-to-treat
population.
Secondary outcome
Secondary endpoints are progression-free survival, response to chemotherapy of
the primary tumour compared to the response of metastases, systemic therapy
related toxicity, surgery related morbidity and mortality (30 and 90 days),
quality of life (QoL), interval between randomization and initiation of
systemic treatment, cost-benefit analysis, patients requiring resection of the
primary tumour in the non-resection arm, and overall survival in patients in
whom treatment according to protocol was initiated (i.e. having received at
least one cycle of systemic treatment in arm A, and surgery in arm B). Patients
without recurrence and alive at the time of the analysis will be included as
censored data. PFS curves will be constructed by means of the Kaplan Meier
method. Comparisons of PFS curves will performed by mean of the Logrank test.
Similar methods will be used to analyse the duration of survival.
Analyses will be done in eligible patients according to the intention-to-treat
principle.
Background summary
The clinical benefit of resection of the primary tumour in patients with
synchronous unresectable metastases is not known. In the literature studies
usually describe retrospective selected patients with synchronous metastases
treated with or without resection of the primary tumour. All these studies are
biased in patient selection and there are no prospective randomized studies on
this topic. In patients with few or absent symptoms of the primary tumour,
arguments both in favor and against initial resection have been presented, and
therefore a randomized trial is warranted.
Study objective
The primary objective is overall survival (OS).
Secondary objectives are progression free survival (PFS), grade 3 and 4
chemotherapy related toxicity, surgery related morbidity and mortality (30 day
and 90 day), quality of life (QoL), number of patients who undergo secondary
surgery of initially irresectable metastases, number of patients who never
receive systemic therapy after resection of the primary tumour, interval
between randomization and initiation of systemic treatment, cost-benefit
analysis, patients requiring resection of the primary tumour in the
non-resection arm, patients requiring stenting or radiotherapy for symptom
palliation, overall survival in patients in whom treatment according to
protocol was initiated (i.e. having received at least one cycle of systemic
treatment in arm A, and surgery in arm B).
Translational research will be performed on prognostic/predictive markers
(resected tumour tissue, and in blood samples, i.e. angiogenic factors, and
sCD95L levels).
Study design
Patients with synchronous metastatic colon cancer or rectum cancer with few or
absent symptoms of their primary tumour are randomized 1:1 between systemic
treatment without resection of the primary tumour and resection of the primary
tumour followed by systemic treatment
Intervention
resection of the primary tumour
Study burden and risks
Both study arms are used in daily practice and therefore there are no
additional risks. Until this study has taken place, it is not clear which
strategy is best.
p/a IKNL Godebaldkwartier 419
Utrecht 3511 DT
NL
p/a IKNL Godebaldkwartier 419
Utrecht 3511 DT
NL
Listed location countries
Age
Inclusion criteria
Histological proof of colorectal cancer
Resectable primary tumour in situ with unresectable distant metastases
No indication for neo-adjuvant (chemo)radiation.
No severe signs or symptoms related to the primary tumour (i.e. severe
bleeding, obstruction, severe abdominal pain) that require immediate surgery or
other symptomatic treatment (e.g. stenting) (see 6.4 for exceptions)
No prior systemic treatment for advanced disease
Age >= 18 years
WHO performance status 0-2
Laboratory values obtained <= 4 weeks prior to randomization: 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)
Expected adequacy of follow-up
Written informed consent
Unidimensionally measurable disease (* 1 cm on CT scan or * 2 cm on chest
X-ray; liver ultrasound is not allowed, according to RECIST 1.1)
CT abdomen performed <= 4 weeks prior to randomization
Exclusion criteria
Pregnancy, lactation
Unresectable primary tumour (i.e. neurovascular encasement, substantial
ingrowth in pancreatic head), or any condition preventing the safety or
feasibility of resection of the primary tumour, i.e. massive ascites or
extensive peritoneal disease
Second primary malignancy within the past 5 years with the exception of
adequately treated in situ carcinoma of any organ or basal cell carcinoma of
the skin
Any medical condition that prevents the safe administration of systemic
treatment
Previous intolerance of fluoropyrimidines, known complete dihydropyrimidine
dehydrogenase (DPD) deficiency
(Planned) radical resection of all metastatic disease
Uncontrolled hypertension, i.e. values consistently > 150/100 mmHg
Use of * 3 antihypertensive drugs
Significant cardiovascular disease < 1 yr before randomization (symptomatic
congestive heart failure, myocardial infarction, unstable angina pectoris,
serious uncontrolled cardiac arrhythmia, cerebrovascular event)
Chronic active infection
Concurrent treatment with any other anti-cancer therapy as described per
protocol
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL38155.091.11 |