Irinotecan/Cetuximab Followed by XELOX/Cetuximab vs the Reverse Sequence in Metastatic CRC

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00755534
• Other study ID #: CT/05.31
• Status: Terminated
• Phase: Phase 2
• First received: September 18, 2008
• Last updated: February 12, 2013
• Start date: November 2008
• Est. completion date: November 2008

Study information

• Verified date: February 2013
• Source: Hellenic Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Irinotecan
Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression
• Capecitabine
Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression
• Cetuximab
Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression
• Oxaliplatin
Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression

Locations

Country	Name	City	State
Greece	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis
Greece	"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Athens
Greece	401 Military Hospital of Athens	Athens
Greece	Air Forces Military Hospital of Athens	Athens
Greece	IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens
Greece	University Hospital of Heraklion, Dep of Medical Oncology	Heraklion	Creta
Greece	State General Hospital of Larissa	Larissa
Greece	"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology	Piraeus
Greece	"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology	Thessaloniki
Greece	Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
Hellenic Oncology Research Group	University Hospital of Crete

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time To Progression		1 year	No
Secondary	Objective Response Rate		Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)	No
Secondary	Toxicity profile		Toxicity assessment on each chemotherapy cycle	Yes
Secondary	1 year Survival and Overall Survival		Probability of 1-year survival (%)	No
Secondary	Correlation of the molecular characteristics of the tumor with the clinical outcome		Corralation after the end of chemotherapy	No