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

Primary Purpose

Colorectal Cancer

Status
Terminated
Phase
Phase 2
Locations
Greece
Study Type
Interventional
Intervention
Irinotecan
Capecitabine
Cetuximab
Oxaliplatin
Sponsored by
Hellenic Oncology Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Metastatic colorectal cancer, Second line, Irinotecan, Cetuximab (Erbitux), Capecitabine (Xeloda)

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Irinotecan+Erbitux -> XELOX+Erbitux

XELOX+Erbitux ->Irinotecan+Erbitux

Outcomes

Primary Outcome Measures

Time To Progression

Secondary Outcome Measures

Objective Response Rate
Toxicity profile
1 year Survival and Overall Survival
Correlation of the molecular characteristics of the tumor with the clinical outcome

Full Information

First Posted
September 18, 2008
Last Updated
February 12, 2013
Sponsor
Hellenic Oncology Research Group
Collaborators
University Hospital of Crete
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1. Study Identification

Unique Protocol Identification Number
NCT00755534
Brief Title
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

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Terminated
Why Stopped
Due to poor accrual
Study Start Date
November 2008 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hellenic Oncology Research Group
Collaborators
University Hospital of Crete

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Metastatic colorectal cancer, Second line, Irinotecan, Cetuximab (Erbitux), Capecitabine (Xeloda)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Irinotecan+Erbitux -> XELOX+Erbitux
Arm Title
2
Arm Type
Experimental
Arm Description
XELOX+Erbitux ->Irinotecan+Erbitux
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
CPT-11, Campto
Intervention Description
Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin, LoHP
Intervention Description
Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression
Primary Outcome Measure Information:
Title
Time To Progression
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective Response Rate
Time Frame
Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
Title
Toxicity profile
Time Frame
Toxicity assessment on each chemotherapy cycle
Title
1 year Survival and Overall Survival
Time Frame
Probability of 1-year survival (%)
Title
Correlation of the molecular characteristics of the tumor with the clinical outcome
Time Frame
Corralation after the end of chemotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Souglakos, MD
Organizational Affiliation
University Hospital of Crete
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Heraklion, Dep of Medical Oncology
City
Heraklion
State/Province
Creta
Country
Greece
Facility Name
University General Hospital of Alexandroupolis, Dep of Medical Oncology
City
Alexandroupolis
Country
Greece
Facility Name
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
City
Athens
Country
Greece
Facility Name
401 Military Hospital of Athens
City
Athens
Country
Greece
Facility Name
Air Forces Military Hospital of Athens
City
Athens
Country
Greece
Facility Name
IASO" General Hospital of Athens, 1st Dep of Medical Oncology
City
Athens
Country
Greece
Facility Name
State General Hospital of Larissa
City
Larissa
Country
Greece
Facility Name
"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology
City
Piraeus
Country
Greece
Facility Name
"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
City
Thessaloniki
Country
Greece
Facility Name
Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki
City
Thessaloniki
Country
Greece

12. IPD Sharing Statement

Learn more about this trial

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

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