Clinical trial NCT01858662: Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors
Official title: Randomised Phase 2 Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
Liver
cetuximab
Pathological response
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Grand Hôpital de Charleroi
First posted: 2013-05-21
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with cetuximab combined with FOLFOX or FOLFIRI regimen in a prospective cohort (RAS and B-RAF WT tumors) and to correlate this response with patient's outcome.

Detailed description: This is a phase II , openlabel, randomized study in patients with confirmed diagnosis of potentially or borderline resectable metastatic colorectal adenocarcinoma (RAS and B-RAF WT tumors ), who have not received prior chemotherapy for their metastatic disease.

The study is designed to compare pathological responses observed after pre-operative chemotherapy cetuximab with FOLFOX or FOLFIRI.

Eligibility criteria: Inclusion Criteria:

1. Female or male patients with at least 18 years at the time the informed consent is signed
2. ECOG performance status 0 or 1
3. Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type RAS and B-RAF tumor status.
4. Patients with potentially resectable metastatic disease at diagnosis and for whom a chemotherapy first in a curative intent is recommended . Resectability could be planed in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors.
5. Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC.
6. Extra hepatic metastatic location is limited to 1 site.
7. Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion.
8. Adequate haematological, renal and hepatic function as follows:

   Haematological:

   haemoglobin \>9g/dl Neutrophils \> 1.5 x 109/L Platelets \> 100 x 109/L

   Renal:

   Creatinine\< 1.5 x ULN (Upper Limit of Normal)

   Hepatic:

   Bilirubin \< or equal 1.5 X ULN AST (Aspartate Aminotransferase),and ALT (Alanine Aminotransferase)\< or equal 5 x ULN, Phos Alc\< or equal 5 x ULN
9. Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
10. Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
11. Life expectancy of at least 3 months without any active treatment.

Exclusion Criteria:

* 1.Definitively non resectable mCRC at diagnosis
* 2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion.
* 3.Prior utilization of cetuximab, panitumumab (or other anti-EGFR (epidermal growth factor receptor)therapy).
* 4.Previous radiotherapy delivered to the upper abdomen.
* 5 Non mesurable disease( RECIST 1.1 criteria)
* 6.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
* 7.Prior major liver resection: remnant liver \< 50% of the initial liver volume.
* 8.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
* 9.Concurrent central nervous systems metastases
* 10.Peripheric neuropathy ≥ grade 2.
* 11.Interstitial lung disease
* 12.Pregnant or breast feeding.
* 13.The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix.

Primary outcomes:
measure: Major Pathological Response Rate
timeFrame: Average 3 months (after resection of metastases)
Secondary outcomes:
measure: progression free survival
timeFrame: at 6 months and at 12 months after randomization
measure: Overall survival
timeFrame: At the end of the study
measure: Clinical response rate
timeFrame: at time of surgery -
measure: Metabolic response rate
timeFrame: At time of surgery - average 3 months
measure: post operative complications
timeFrame: one month after surgery
measure: Curative resection rate
timeFrame: At time of surgery
measure: Chemotherapy-associated hepatotoxicity:
timeFrame: at time of surgery
Other outcomes:
Locations:
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
state: Hainaut
city: Bouge
country: Belgium
facility: clinique Saint Luc
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc - UCL
city: La Louvière
country: Belgium
facility: Centre Hospitalier Jolimont Lobbes
city: Liège
country: Belgium
facility: CHU liège (Sart Timan)
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre Ottignies
city: Yvoir
country: Belgium
facility: CHU-UCL Dinant-Godinne
Study officials:
affiliation: Cliniques universitaires Saint-Luc - UCL
name: Marc Van den Eynde, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Grand Hôpital de Charleroi
name: Javier Carrasco, MD PhD
role: PRINCIPAL_INVESTIGATOR
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