Phase II Study to Evaluate Safety and Efficacy of Cetuximab in Combination With XELOX for 12 Weeks Followed by Maintenance Treatment With Cetuximab Plus Capecitabine as First-line Treatment in Elderly Patients With Metastatic Colorectal Cancer.

• ClinicalTrials.gov Identifier: NCT00531115
• Recruitment Status: Terminated
• First Posted: September 18, 2007
• Last Update Posted: February 20, 2013
• Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Tracking Information

• First Submitted Date: September 17, 2007
• First Posted Date: September 18, 2007
• Last Update Posted Date: February 20, 2013
• Study Start Date: November 2007
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 18, 2010): Confirmed objective response rate [ Time Frame: 2007-2009 ]
• Original Primary Outcome Measures (submitted: September 17, 2007): Confirmed objective response rate
• Change History: Complete list of historical versions of study NCT00531115 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 18, 2010)

• Disease control, Time to progression, progression-free survival,Time to treatment failure,Determine time to onset of response, Duration of response, Overall survival, To determine biologic prognostic factors [ Time Frame: 2007-2009 ]
• Treatment safety [ Time Frame: 2007-2009 ]

• Original Secondary Outcome Measures (submitted: September 17, 2007): Disease control, Treatment safety, Time to progression, progression-free survival,Time to treatment failure,Determine time to onset of response, Duration of response, Overall survival, To determine biologic prognostic factors
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II Study to Evaluate Safety and Efficacy of Cetuximab in Combination With XELOX for 12 Weeks Followed by Maintenance Treatment With Cetuximab Plus Capecitabine as First-line Treatment in Elderly Patients With Metastatic Colorectal Cancer.
• Official Title: Multicentre, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Cetuximab in Combination With Oxaliplatin and Capecitabine (XELOX) for 12 Weeks Followed by Maintenance Treatment With Cetuximab Plus Capecitabine as First-line Treatment in Elderly Patients With Metastatic Colorectal Cancer.
• Brief Summary: The purpose of this study is to determine confirmed objective response rate to combination therapy with cetuximab plus XELOX for 4 cycles followed by maintenance treatment with cetuximab plus capecitabine as first line treatment in elderly patients with metastatic colorectal cancer

Detailed Description

• This open-label, non-controlled, multicentre, phase II study will recruit 53 elderly patients with diagnosis of metastatic colorectal cancer.
• All patients will receive 4 cycles of treatment with cetuximab plus XELOX followed by cetuximab plus capecitabine as maintenance therapy until progression of disease, occurrence of unacceptable toxicity to the study drugs, or withdrawal of consent by the patient.
• The planned duration of a cycle is 3 weeks.
• Cetuximab therapy will not be delayed for chemotherapy-related toxicity and vice versa. If patients benefit from combination therapy, but develop unacceptable intolerance to oxaliplatin and/or capecitabine, cetuximab may be continued in combination with the other chemotherapy drug and/or as a single agent. In case of cetuximab intolerance, patients should continue with chemotherapy treatment until progression disease.

• Evaluations:

  • Efficacy data (response rate, progression-free survival, duration of response and survival) and safety data will be collected. The investigators will assess responses to treatment.
  • When the treatment is stopped either because of disease progression or occurrence of unacceptable toxicity, the patients will enter a follow-up period where the progression-free survival, the subsequent lines of treatment and the survival data will be collected every 12 weeks.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

Drug: cetuximab 5mg/ml

Weekly administration of Cetuximab (initial infusion of 400 mg/m2 for 120 minutes followed by subsequent maintenance doses of 250 mg/m2 for 60 minutes) Oxaliplatin. 130 mg/m2 every three weeks. on day 1 for 4 cycles Capecitabine. 1000 mg/m2 twice daily (2.000 mg/m2 total daily dose) or 750 mg/m2 if Cl Cr=30-50 ml/min (1500 mg/m2 total daily dose) for two weeks (on days 1 to 14) followed by one week of rest (on days 15 to 21).

The patients will receive 4 cycles of cetuximab plus combination chemotherapy administered every 3 weeks in order to achieve a noticeable response. Then, oxaliplatin treatment will be stopped after a maximum of 4 infusions to prevent appearance of neuropathy and then followed by capecitabine 2 weeks out of 3, and cetuximab weekly as maintenance treatment.

Study Arms

Experimental: 1

Intervention: Drug: cetuximab 5mg/ml

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 18, 2010): 28
• Original Estimated Enrollment (submitted: September 17, 2007): 53
• Actual Study Completion Date: April 2009
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed written informed consent before any study related activities are carried out
• Men and women >= 70 years.
• Histologically confirmed diagnosis of CRC.
• Non-resectable and/or non-operable metastatic colorectal carcinoma.
• Presence of at least one lesion by two-dimensional measurement; index lesions should not be in a region with previous irradiation.
• Availability of tumor tissue for immunohistochemical analysis
• Karnofsky functional status >= 80% at the time of enrollment in the study.
• Life expectancy greater than 3 months.
• Patients will not have received chemotherapy for advanced or metastatic disease. Patients with the following characteristics will be included: 1. Recurrence after neoadjuvant and/or adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free interval > 12 months following conclusion of treatment. 2. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment. 3. De novo diagnosis of disease.
• Proper hematological, renal and hepatic function,

Exclusion Criteria:

• Documented or suspected cerebral and/or leptomeningeal metastases.
• Surgery (excluding biopsy for diagnosis) and/or radiotherapy during the 4 weeks prior to inclusion in the study.
• Chronic, concomitant systemic immunotherapy, chemotherapy, or hormonal treatment for cancer.
• Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment.
• Participation in another clinical trial with medication in the past 30 days
• Prior participation in a study in which treatment with cetuximab may be assigned (whether or not treatment with cetuximab is received).
• Prior malignant tumor in the past 5 years, except for history of adequately treated basal cell skin cancer or pre-invasive cervical cancer .
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome or history of inflammatory intestinal disease, acute or subacute intestinal occlusion or other disease which could alter drug absorption.
• Evidence of grade 3 or 4 allergic reaction to any treatment components or other fluoropyrimidines.
• Clinically relevant peripheral neuropathy.
• Clinically significant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of decompensation of heart failure or arrhythmia.
• Serious active infections (requiring intravenous antibiotics), including active tuberculosis and diagnosed HIV.
• Known abuse of alcohol/drugs.
• Legal incapacity or limited legal capacity.
• Any medical or psychological disorder which, in the opinion of the investigator, does not allow the patient to conclude the study or sign the informed consent.

• Patients catalogued as delicate or "frail" for compliance with any of the following criteria

  • Dependence in one or more activities of daily life according to the Katz Activity of Daily Living (ADL) scale.
  • 3 or more comorbid entities based on evaluation of the presence of the following processes: congestive heart failure; valvular heart disease; coronary artery disease; obstructive or restrictive chronic pulmonary disease; cerebrovascular disease; peripheral neuropathies; chronic renal failure; hypertension; diabetes; concomitant neoplasms; collagen vascular diseases; and incapacitating arthritis.
  • Presence of geriatric syndromes: moderate-severe dementia; delirium in situation of stress (urinary or respiratory infection, angina or drugs); moderate-severe depression that interferes with usual activity of patient; frequent falls (3 or more per month); lack of care (Who could help him or her in the event of an emergency?); urinary incontinence in the absence of stress, infection, diuretics or prostatic hyperplasia; fecal incontinence in the absence of diarrhea or laxatives; osteoporotic fractures of long bones or vertebral crush.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00531115
• Other Study ID Numbers: TTD-06-05; EudraCT Nº: 2006-007062-11
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Study Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Collaborators: Merck Sharp & Dohme Corp.

Investigators

• Study Chair: Javier Sastre; H. Clinico San Carlos. Madrid. Spain

• PRS Account: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Verification Date: February 2013