E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral mucositis (OM) associated with multi-cycle chemotherapy with fluoropyrimidine containing regimens |
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MedDRA Classification |
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 |
To evaluate the effect of palifermin on the incidence of Grade ≥ 2 OM induced by adjuvant chemotherapy in subjects with stage 2B and 3 locally advanced colon cancer in cycle 1, when administered as a single dose of 120 μg/kg three days prior to each 4-week cycle of 5-FU and leucovorin
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of palifermin administered as a single dose of 120 µg/kg IV before each cycle of 5-FU and leucovorin
To evaluate the effect of palifermin on patient-reported mouth and throat soreness (MTS)
To evaluate the duration of Grade ≥ 2 OM
To evaluate 5-FU dose reductions/delays
To evaluate the long-term effects of palifermin on disease outcome and survival
To evaluate the incidence of Grade ≥ 2 OM in cycle 2 |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Written informed consent
• Histologically confirmed diagnosis of colon adenocarcinoma
• Newly diagnosed stage 2B or 3 (AJCC staging criteria) resected colon carcinoma and a candidate for 5-FU/LV treatment
• Subjects 18 years of age or older
• ECOG performance status ≤ 1
• Baseline Laboratory Assessments: Hemoglobin (Hgb) ≥ 10 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L Platelet count ≥ 100 x 10e9/L Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) Serum creatinine ≤ 2.0 mg/dL Serum AST ≤ 5x ULN
• Females of childbearing potential: negative serum or urine pregnancy test
• Subjects with reproductive capability must agree to practice adequate contraception methods
• Absence of other serious concurrent medical illness
• Willingness to participate in subsequent long-term follow up study |
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E.4 | Principal exclusion criteria |
• Previous therapy (e.g. chemotherapy, radiotherapy or biological therapy) for colon cancer, other than surgical tumor resection
• Presence or history of any other primary malignancy
• Presence of active or chronic OM or xerostomia
• Presence of active diarrhea > grade 1 according to CTCAE v. 3 grading criteria within 3 days prior to randomization
• History of pancreatitis
• Four weeks or less since completion of treatment using an investigational product or device in another clinical study or presence of any unresolved toxicity from previous treatment
• Subjects who would be unwilling/unable to complete daily patient-reported outcome (PRO) questionnaires
• Pregnant or breast-feeding women
• Subjects of childbearing potential not using adequate contraceptive precautions
• Known sensitivity to any of the products administered during dosing, including E coli-derived products
• Known to be sero-positive for human immunodeficiency virus (HIV) or Hepatitis C Virus (HCV)
• Previous treatment on this study or with other keratinocyte growth factors
• Psychological, social, familial, or geographical reasons that would prevent regular follow-up
• Compromised ability of the subject to give written informed consent and/or to comply with study procedures
• Refusal to sign an informed consent form to participate in this study or, if applicable, refusal to sign the hospital information release |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of grade ≥ 2 (World Health Organization [WHO] scale) OM in cycle 1 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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After the treatment phase subjects will be monitored for disease progression,2nd primary tumors,malignancies & survival. Annually from randomization (until lost to follow-up or death) subjects will have LTFU visits (physical exam & serum CEA level performed yearly after yr 5).Amgen believes it appropriate to submit EOS notifications at the end of the active treatment phase & commit to submit information obtained during LTFU that changes the risk benefit ratio through normal safety reporting.
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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |