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

This study has been terminated.
(Due to poor accrual)
Sponsor:
Collaborator:
University Hospital of Crete
Information provided by (Responsible Party):
Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00755534
First received: September 18, 2008
Last updated: February 12, 2013
Last verified: February 2013
  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 2

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

Resource links provided by NLM:


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 ]

Enrollment: 68
Study Start Date: November 2008
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Irinotecan+Erbitux -> XELOX+Erbitux
Drug: Irinotecan
Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression
Other Names:
  • CPT-11
  • Campto
Drug: Capecitabine
Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression
Other Name: Xeloda
Drug: Cetuximab
Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression
Other Name: 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:
  • CPT-11
  • Campto
Drug: Capecitabine
Capecitabine (p.o) 2000 mg/m2 (1000 mg/m2 x 2) on day 1-7 every 2 weeks until progression
Other Name: Xeloda
Drug: Cetuximab
Cetuximab(IV) 500 mg/m2 on day 1 every two weeks until progression
Other Name: Erbitux
Drug: Oxaliplatin
Oxaliplatin (I.V) 85 mg/m2 on day 1 every two weeks until progression
Other Names:
  • Eloxatin
  • LoHP

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Greece
University Hospital of Heraklion, Dep of Medical Oncology
Heraklion, Creta, Greece
University General Hospital of Alexandroupolis, Dep of Medical Oncology
Alexandroupolis, Greece
IASO" General Hospital of Athens, 1st Dep of Medical Oncology
Athens, 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
State General Hospital of Larissa
Larissa, Greece
"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology
Piraeus, Greece
Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki
Thessaloniki, Greece
"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
Thessaloniki, Greece
Sponsors and Collaborators
Hellenic Oncology Research Group
University Hospital of Crete
Investigators
Principal Investigator: John Souglakos, MD University Hospital of Crete
  More Information

No publications provided

Responsible Party: Hellenic Oncology Research Group
ClinicalTrials.gov Identifier: NCT00755534     History of Changes
Other Study ID Numbers: CT/05.31
Study First Received: September 18, 2008
Last Updated: February 12, 2013
Health Authority: Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:
Metastatic colorectal cancer
Second line
Irinotecan
Cetuximab (Erbitux)
Capecitabine (Xeloda)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Irinotecan
Capecitabine
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 21, 2014