Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NCT-2009-11-02-1031
Study information
Scientific title
In vivo response monitoring of treatment with the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in metastatic colorectal cancer: a single centre phase II study
Acronym
REMOTUX
Study hypothesis
Due to therapeutic advances including several new active agents, the prognosis for patients with metastatic colorectal cancer has improved during the last years from a median survival of about 12 months with fluorouracil alone to almost 24 months with combination therapies. But obviously, the prognosis still remains limited and patients have to undergo several therapeutic regimens with a considerable rate of side effects. To date, there is scarce data concerning early response assessment in metastastic colorectal cancer under treatment with cetuximab. In order to achieve more information about the early changes in both tumour glucose metabolism and tumour vascularisation and to evaluate its prognostic relevance for early clinical response, we aim to strictly monitor the effects of cetuximab on both parameters during a short-term single agent therapy with cetuximab. The achieved information may be helpful to early identify those subgroups of wild-type KRAS patients who respond to treatment with cetuximab. This knowledge would mean a step forward to "tailoring" individual treatment schedules based on the different biological tumour backgrounds.
Ethics approval
Not provided at time of registration
Study design
Prospective open-label single-arm single-centre early exploratory prognostic study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Metastatic colorectal cancer
Intervention
Treatment as well as routine and trial specific examinations will be conducted according to the following register:
Baseline: study registration followed by, for imaging analysis, fluorine-18 fluordeoxyglucose positron emission tomography (18F-FDG PET-CT) scan and contrast-enhanced ultrasound
Day 1: treatment with cetuximab 400 mg/m^2 body surface area (bsa) will be started
Day 8: treatment will be continued with cetuximab 250 mg/m^2 bsa
Day 14 (end of treatment): imaging analysis with 18F-FDG PET-CT and a contrast-enhanced ultrasound examination
Day 56: evaluation of clinical response with a routine CT-scan
Between day 14 and day 56, patients will be treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma.
Intervention type
Drug
Phase
Phase II
Drug names
Cetuximab
Primary outcome measure
To evaluate the prognostic relevance of relative changes in SUV (delta-SUV; as measured in 18F-FDG PET-CT at day 14 versus baseline) for early clinical response (as defined by Response Evaluation Criteria In Solid Tumours [RECIST], measured at day 56) during short-term single agent treatment with the EGFR-mAB cetuximab.
Secondary outcome measures
1. To investigate duration of PFS as well as the influence of changes in individual SUV and of early clinical response on PFS
2. To investigate duration of overall survival (OS)
3. The assessment of antivascular/antiangiogenic effects of cetuximab by contrast-enhanced ultrasound
This clinical trial will include an accompanying research component involving collection of biological samples for pseudonymised analyses. These will comprise sequential serum protein marker assessments (e.g., multiplex cytokine immune monitoring) as well as baseline analysis of tumour proteins and tumour genes, (e.g., PTEN expression, mutations in EGFR dependent downstream kinases like PI-3-kinase, BRAF and EGFR gene expression as measured by fluorescence-in-situ hybridisation). Patients may participate in this study even if they choose not to participate in this component.
Overall trial start date
01/01/2010
Overall trial end date
01/09/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed metastatic colorectal cancer
2. KRAS-wildtype status of the tumour
3. No history of therapy with an EGFR targeting agent
4. No history of previous chemotherapy for advanced disease
5. Measurable tumour lesion with a diameter no smaller than 1.0 cm detected by computed tomography (CT), magnetic resonance imaging (MRI) or ultrasound
6. For contrast-enhanced ultrasound: metastases no smaller than 2.0 cm detected by ultrasound
7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 or Karnofsky performance scale minimum 60%
8. Life expectancy greater than 12 weeks
9. Age greater than or equal to 18 years, either sex
10. Adequate haematologic, renal and hepatic function
11. Ability of the patient to understand the character and individual consequences of this clinical trial
12. Written informed consent (must be available before enrolment in the trial)
13. For women and men with childbearing potential adequate double barrier contraception, for women: negative pregnancy test
14. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
35
Participant exclusion criteria
1. Any contraindications for chemotherapy according to the Folfiri regimen
2. Non-curatively treated malignancy within the last 5 years
3. Uncontrolled or insulin-depending diabetes mellitus
4. Evidence of central nervous system (CNS) metastases
5. Uncontrolled infection
6. Significant cardiac disease (unstable angina pectoris or cardia symptoms according to New York Heart Association [NYHA] classification III or IV)
7. Active serious illness which renders the patient unsuitable for study entrance or multiple blood sampling
8. Pregnancy and lactation
9. History of hypersensitivity to cetuximab or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
10. Participation in other clinical trials or observation period of competing trials, respectively
11. No patient will be allowed to enrol in this trial more than once
Recruitment start date
01/01/2010
Recruitment end date
01/09/2014
Locations
Countries of recruitment
Germany
Trial participating centre
Im Neuenheimer Feld 350
Heidelberg
69120
Germany
Sponsor information
Organisation
University of Heidelberg (Germany)
Sponsor details
c/o Irmtraut Gürkan
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Merck Pharma GmbH (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list