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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: Capecitabine; Drug: Cetuximab; Drug: Oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Irinotecan+Erbitux -> XELOX+Erbitux	Drug: Irinotecan; Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression; Other Names: Campto; CPT-11; Drug: Capecitabine; Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression; Other Names: Xeloda; Drug: Cetuximab; Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression; Other Names: Erbitux; Drug: Oxaliplatin; Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression; Other Names: Eloxatin; LoHP
Experimental: 2; XELOX+Erbitux ->Irinotecan+Erbitux	Drug: Irinotecan; Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression; Other Names: Campto; CPT-11; Drug: Capecitabine; Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression; Other Names: Xeloda; Drug: Cetuximab; Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression; Other Names: Erbitux; Drug: Oxaliplatin; Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression; Other Names: Eloxatin; LoHP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time To Progression	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity profile	Toxicity assessment on each chemotherapy cycle
Objective Response Rate	Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
1 year Survival and Overall Survival	Probability of 1-year survival (%)
Correlation of the molecular characteristics of the tumor with the clinical outcome	Corralation after the end of chemotherapy

Collaborators and Investigators

• Sponsor: Hellenic Oncology Research Group
• Collaborators: University Hospital of Crete
• Investigators: Principal Investigator: John Souglakos, MD, University Hospital of Crete

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 18, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Estimate): February 13, 2013
• Last Update Submitted That Met QC Criteria: February 12, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Irinotecan; Metastatic colorectal cancer; Second line; Cetuximab (Erbitux); Capecitabine (Xeloda)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Capecitabine; Oxaliplatin; Irinotecan; Cetuximab
• Other Study ID Numbers: CT/05.31