In vivo response monitoring of treatment with the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in metastatic colorectal cancer

ISRCTN ISRCTN75334801
DOI https://doi.org/10.1186/ISRCTN75334801
Protocol serial number NCT-2009-11-02-1031
Sponsor University of Heidelberg (Germany)
Funder Merck Pharma GmbH (Germany)
Submission date
13/08/2009
Registration date
04/09/2009
Last edited
04/09/2009
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Anne-Katrin Berger
Scientific

Im Neuenheimer Feld 350
Heidelberg
69120
Germany

Study information

Primary study designInterventional
Study designProspective open-label single-arm single-centre early exploratory prognostic study
Secondary study designNon randomised controlled trial
Study type Participant information sheet
Scientific titleIn 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
Study acronymREMOTUX
Study objectivesDue 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(s)Not provided at time of registration
Health condition(s) or problem(s) studiedMetastatic colorectal cancer
InterventionTreatment 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 typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Cetuximab
Primary outcome measure(s)

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.

Key secondary outcome measure(s)

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.

Completion date01/09/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration35
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/01/2010
Date of final enrolment01/09/2014

Locations

Countries of recruitment

  • Germany

Study participating centre

Im Neuenheimer Feld 350
Heidelberg
69120
Germany

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
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