E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Age >18 years. Life expectancy > 12 weeks ECOG performance status ≤ 1 Participants must have normal organ and marrow function. Adequate contraception prior to study entry and for the duration of study participation. Ability to understand and the willingness to sign a written informed consent document.
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E.1.1.1 | Medical condition in easily understood language |
Histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034750 |
E.1.2 | Term | PET scan abnormal |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008452 |
E.1.2 | Term | Chemotherapy multiple agents systemic |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
a) To obtain a preliminary assessment about the activity of the combination by estimating overall survival of the study population at a fixed time point (6 months) b) To compare as an exploratory analysis the overall survival of metabolic responders versus non-responders.
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E.2.2 | Secondary objectives of the trial |
• Determine the progression-free survival of the study population receiving the study regimen. • Determine the objective response rate of the study population receiving the study re-gimen, as assessed by standard imaging. • Describe the adverse reactions associated with the study regimen in the study population. • Determine the correlation of early metabolic response, as assessed by FDG-PET/CT immediately before the first and the second cycles of treatment with the study regi-men, with overall survival, progression-free survival, and response rate. • Determine the correlation of growth modulation index (GMI), defined as the time to progression under the study regimen over the time to progression under the latest prior regimen administered to the patient, with overall survival and progression-free survival.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participants must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. • All standard chemotherapy agents (fluoropyrimidines, irinotecan, and oxaliplatin) and monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) are allowed as administered therapy before study entry. No more than two lines of treatment for metastatic or recurrent disease are allowed, except for patients with KRAS-wt tumors, for which third line with anti-EGFR agents is allowed. • Age over 18 years. • Life expectancy of greater than 12 weeks. • ECOG performance status ≤ 1. • Participants must have normal organ and marrow function as defined below: • Leukocytes > 3,000/mcL • Absolute neutrophil count > 1,500/mcL • Platelets > 100,000/mcL • total bilirubin within 2 × normal institutional limits • AST/ALT/PAKL levels < 5 × institutional upper limit of normal • creatinine within 2 × normal institutional limits or creatinine clearance > 35mL/min • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. • Ability to understand and the willingness to sign a written informed consent document.
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E.4 | Principal exclusion criteria |
Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. • Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. • Participants may not be receiving any other study agents. • Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib or capecitabine. • Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months, or major surgery within four weeks. • Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. • Pregnant women are excluded from this study because sorafenib and capecitabine are antitumor agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with sorafenib or capecitabine, breastfeeding should be discontinued if the mother is treated with sorafenib or capecitabine. These potential risks may also apply to other agents used in this study. • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
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E.5 End points |
E.5.1 | Primary end point(s) |
a) To obtain a preliminary assessment about the activity of the combination by estimating overall survival of the study population at a fixed time point (6 months) b) To compare as an exploratory analysis the overall survival of metabolic responders versus non-responders.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
completion of study : september 2011 6 months overal survival : march 2012 |
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E.5.2 | Secondary end point(s) |
• To estimate the progression-free survival distribution of the study population • To determine the objective response rate of the study population as assessed by standard imaging. • To describe the adverse reactions associated with the study regimen in the study population. • To determine the correlation of early metabolic response, as assessed by FDG-PET/CT immediately before the first and the second cycles of treatment with the study regimen, with overall survival, progression-free survival, and response. • To determine the correlation of growth modulation index (GMI), defined as the time to progression under the study regimen over the time to progression under the latest prior regimen administered to the patient, with overall survival and progression-free survival.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
completion of study : september 2011 6 months overal survival : march 2012 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
metabolic imaging of tumor response |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |