| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10028130 | | E.1.2 | Term | Mucositis oral | | E.1.2 | System Organ Class | 100000004856 | |
| 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 | |
| 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
To evaluate the incidence of Grade ≥ 2 OM in cycle 2
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
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Disease Related
• Histologically confirmed diagnosis of colon adenocarcinoma
• Newly diagnosed stage 2B or 3 (AJCC staging criteria; see Appendix F) resected colon carcinoma and a candidate for 5-FU/LV treatment
Demographic
• 18 years of age or older
• ECOG performance status ≤ 1
Baseline Laboratory
• Hemoglobin (Hgb) ≥ 10 g/dL without transfusional support or growth factor use in the 4 weeks before study randomization
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor use in the 2 weeks before study randomization
• Platelet count ≥ 100 x 109/L
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Serum creatinine ≤ 2.0 mg/dL
• Serum AST ≤ 5 x ULN
• Females of childbearing potential: negative serum or urine pregnancy test
Ethical
• Subject must give written informed consent before participating in any study-specific procedure
General
• 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 | |
| E.4 | Principal exclusion criteria | Disease Related
• Previous therapy (eg, 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 oral mucositis or xerostomia
• Presence of active diarrhea > grade 1 according to CTCAE v. 3 grading criteria within three days prior to randomization
• History of pancreatitis
Medication/Prior Treatment
• 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
• Known sensitivity to any of the products administered during dosing, including E. coli-derived products
• Previous treatment on this study or with other keratinocyte growth factors
Laboratory
• Known to be sero-positive for human immunodeficiency virus (HIV) or Hepatitis C Virus (HCV)
General
• Subjects who would be unwilling/unable to complete daily patient-reported outcome questionnaires
• Subjects of childbearing potential not using adequate contraceptive precautions
• Pregnant or breast-feeding women
• 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 form | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Incidence of grade ≥ 2 (WHO scale) OM in cycle 1 | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | 1 week (as per assessment at cycle 1) | |
| E.5.2 | Secondary end point(s) | Secondary:
• Incidence of grade ≥ 2 (WHO scale) OM in cycle 2
• Average MTS score (OMDQ Question 2) in cycle 1
• Average MTS score (OMDQ Question 2) in cycle 2
• Incidence of 5-FU dose reductions and dose delays in cycle 2
• Duration of Grade ≥ 2 (WHO scale) OM in cycle 1
• Duration of Grade ≥ 2 (WHO scale) OM in cycle 2 | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | week 1 and week 2
After completion of, or withdrawal from, the treatment phase, subjects
will continue onto the long-term follow-up phase and will be monitored
for disease progression, second primary tumors, other malignancies
and overall survival until considered lost to follow-up, death, or for up
to 5 years from the last subject randomized. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| 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 | No |
| 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) | 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 | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 | No |
| 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 | | After completion of, or withdrawal from, the treatment phase, subjects will continue onto the long-term follow-up phase and will be monitored for disease progression, second primary tumors, other malignancies and overall survival until considered lost to follow-up, death, or for up to 5 years from the last subject randomized. | |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| 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 |
