Clinical trial NCT00755534: Irinotecan/Cetuximab Followed by XELOX/Cetuximab vs the Reverse Sequence in Metastatic CRC
Official title: A Parallel Phase II Study With Irinotecan/Cetuximab (Until PD) Followed by XELOX/Cetuximab (Until PD) vs the Reverse Sequence in Metastatic CRC With Previous Benefit on Irinotecan/Bevacizumab Based Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Metastatic colorectal cancer
Second line
Irinotecan
Cetuximab (Erbitux)
Capecitabine (Xeloda)
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2008-09-19
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II study will evaluate which is the best way to administer cetuximab after recurrence in 1st line irinotecan+bevacizumab based treatment and to obtain results of the efficacy of the oxaliplatin+cetuximab combination as 2nd line treatment.

Detailed description: Because of the recent advances in the field of systemic chemotherapy for mCRC, like irinotecan, oxaliplatin, capecitabine, and targeted agents (Cetuximab, Bevacizumab) mCRC patients have an overall survival that in some cases reaches 25 months.Irinotecan is an inhibitor of the DNA enzyme topoisomerase I, with use in clinical practice for the last 10 years.In a phase II study with mCRC patients resistant to irinotecan based therapy the combination of irinotecan and Cetuximab (an IgG1 anti-EGFR antibody) yielded a response rate of 22.5%.Capecitabine was shown to have improved tolerability and response rate compared with bolus 5-FU, with comparable time to progression and survival.Oxaliplatin has been approved by the FDA for 2nd line treatment in the metastatic CRC setting as a number of trials have shown promising data for response rates, disease stabilization rates,median progression free survival (PFS) and overall survival (OS).KRAS is a predictive marker for clinical benefit from EGFR-based antibody treatment. KRAS is the first molecular marker for selection of a targeted therapy in combination with a standard chemotherapy regimen. Patients with KRAS wild-type tumors have a strong benefit from the administration of cetuximab with better PFS and objective responses.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed locally advanced or metastatic colorectal cancer
* Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
* ECOG performance status ≤ 2
* Age 18 - 72 years
* Patients who have had a CR, PR or SD after 1st line therapy based on Irinotecan+Bevacizumab
* Paraffin block from the primary tumor in order to perform tha mutational analysis of the KRAS gene
* Adequate liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 4 upper normal limit, ALP ≤ 2.5 upper normal limit),renal (Creatinine ≤ 1.5 upper normal limit) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function
* Patients must be able to understand the nature of this study
* Written informed consent

Exclusion Criteria:

* Presence of central nervous system or brain metastases
* Pregnant or lactating woman
* Life expectancy \< 3 months
* Previous radiotherapy within the last 4 weeks or \> 25% of bone marrow or in the field where the treatment target is located
* Peripheral neuropathy grade ≥2
* Known hypersensitivity to Erbitux
* Metastatic infiltration of the liver \>50%
* Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy
* Active infection
* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
* Psychiatric illness or social situation that would preclude study compliance

Primary outcomes:
measure: Time To Progression
timeFrame: 1 year
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
measure: Toxicity profile
timeFrame: Toxicity assessment on each chemotherapy cycle
measure: 1 year Survival and Overall Survival
timeFrame: Probability of 1-year survival (%)
measure: Correlation of the molecular characteristics of the tumor with the clinical outcome
timeFrame: Corralation after the end of chemotherapy
Other outcomes:
Locations:
city: Heraklion
country: Greece
facility: University Hospital of Heraklion, Dep of Medical Oncology
state: Creta
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis, Dep of Medical Oncology
city: Athens
country: Greece
facility: "Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
city: Athens
country: Greece
facility: 401 Military Hospital of Athens
city: Athens
country: Greece
facility: Air Forces Military Hospital of Athens
city: Athens
country: Greece
facility: IASO" General Hospital of Athens, 1st Dep of Medical Oncology
city: Larissa
country: Greece
facility: State General Hospital of Larissa
city: Piraeus
country: Greece
facility: "Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: "Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki
Study officials:
affiliation: University Hospital of Crete
name: John Souglakos, MD
role: PRINCIPAL_INVESTIGATOR
References: