Irinotecan/Cetuximab Followed by XELOX/Cetuximab vs the Reverse Sequence in Metastatic CRC - Full Text View

Sponsors and Collaborators:	Hellenic Oncology Research Group University Hospital of Crete
Information provided by:	Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:	NCT00755534

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: Irinotecan Drug: Capecitabine Drug: Cetuximab Drug: Oxaliplatin	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride Capecitabine Bevacizumab Oxaliplatin Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Hellenic Oncology Research Group:

Primary Outcome Measures:

Time To Progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective Response Rate [ Time Frame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle) ] [ Designated as safety issue: No ]
Toxicity profile [ Time Frame: Toxicity assessment on each chemotherapy cycle ] [ Designated as safety issue: Yes ]
1 year Survival and Overall Survival [ Time Frame: Probability of 1-year survival (%) ] [ Designated as safety issue: No ]
Correlation of the molecular characteristics of the tumor with the clinical outcome [ Time Frame: Corralation after the end of chemotherapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	October 2008
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Irinotecan+Erbitux -> XELOX+Erbitux	Drug: Irinotecan Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression Drug: Capecitabine Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression Drug: Cetuximab Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression Drug: Oxaliplatin Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression
2: Experimental XELOX+Erbitux ->Irinotecan+Erbitux	Drug: Irinotecan Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression Drug: Capecitabine Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression Drug: Cetuximab Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression Drug: Oxaliplatin Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression

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

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00755534

Contacts

Contact: Dora Hatzidaki	+302810392570	dorachat@med.uoc.gr
Contact: Eva Maragkoudaki	+302810392857	dorachat@med.uoc.gr

Locations

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

Sponsors and Collaborators

Hellenic Oncology Research Group

University Hospital of Crete

Investigators

Principal Investigator:

John Souglakos, MD

University Hospital of Crete

More Information

Responsible Party:	Hellenic Oncology Research Group ( John Sougklakos )
Study ID Numbers:	CT/05.31
Study First Received:	September 18, 2008
Last Updated:	September 19, 2008
ClinicalTrials.gov Identifier:	NCT00755534
Health Authority:	Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:

Metastatic colorectal cancer
Second line
Irinotecan
Cetuximab (Erbitux)
Capecitabine (Xeloda)

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Irinotecan
Bevacizumab

Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 13, 2009