E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with metastatic colorectal cancer confined to the liver who underwent R0/1 resection of liver metastases |
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E.1.1.1 | Medical condition in easily understood language |
metastatic colorectal cancer confined to the liver |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The study aims to assess the efficacy of postoperative therapy with FOLFOX plus panitumumab followed by maintenance with panitumumab for 3 months in RAS wild-type patients, compared to the historical data for standard FOLFOX chemotherapy alone, which are verified by a randomised control group without the antibody. |
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E.2.2 | Secondary objectives of the trial |
The study aims to investigate the tolerability of panitumumab-based therapy in the postoperative setting. In addition, predictors of treatment efficacy shall be identified by an evaluation of the molecular pathology of the disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has provided written informed consent.
2. R0/1-resection of liver metastasis, at least four weeks but not longer than 8 weeks ago (submission of the pathologist´s report to exclude R2 resection status is mandatory for randomisation)
3. Histologically confirmed diagnosis of metastatic colorectal cancer confined to the liver
4. RAS wild-type of the tumor, tested in:
• KRAS exon 2 (codons 12/13)
• KRAS exon 3 (codons 59/61)
• KRAS exon 4 (codons 117/146)
• NRAS exon 2 (codons 12/13)
• NRAS exon 3 (codons 59/61)
• NRAS exon 4 (codons 117/146)
5. Age 18 years or older
6. ECOG performance status 0-1
7. Females with child-bearing potential must use adequate contraceptive measures
8. Exclusion of pregnancy
9. Relevant toxicities of previous treatments must have subsided
10. Magnesium ≥ lower limit of normal; Calcium ≥ lower limit of normal
11. Normal cardiac function demonstrated by ECG and echocardiogram (LVEF ≥ 55%)
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
12. Adequate organ function as defined by Table 1:
Table 1: Adequate Hepatic and Renal Function Values
SYSTEM LABORATORY VALUES
Hematologic
ANC (absolute neutrophil count) ≥ 1.5 G/L
Leucocytes > 3.0 G/L
Hemoglobin ≥ 9 g/dL
Platelets ≥ 100 G/L
Hepatic
Albumin ≥ 2.5 g/dL
Serum bilirubin <=2 mg/dL
AST and ALT <= 3 x ULN
Renal
Serum Creatinine <= 1.5 mg/dL
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E.4 | Principal exclusion criteria |
1. Known manifestations of metastatic disease
2. Progression during preoperative treatment
3. RAS mutation of the tumor
4. Contraindication against therapy with 5-Fluorouracil/ folinic acid or oxaliplatin
5. Known intolerability of panitumumab
6. Known DPD deficiency
7. Polyneuropathy > grade 1 (NCI-CTCv4) which precludes the use of oxaliplatin
8. Evidence of ascites or cirrhosis
9. Patient is pregnant or lactating or planning to become pregnant within 6 months after end of treatment
10. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment
11. Has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrolment, or there is an anticipated need for major surgical procedure during the course of the study. This excludes minor surgical procedures like implantation of intravenous portsystems (7 days prior enrolment) or central venous catheters (2 days prior enrolment).
12. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) <=1 year before enrolment/randomisation
13. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
14. Has a concurrent disease or condition that would make the subject inappropriate for study participation or would interfere with the subject’s safety.
15. Has any psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
16. Requires concurrent cancer therapy (chemotherapy, radiation therapy, biologic therapy, immunotherapy, or hormonal therapy) while on study.
17. Requires concurrent treatment with an investigational agent, participation in another clinical trial, or any specifically prohibited medication while on study.
18. Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to 5-Fluorouracil, folinic acid, oxaliplatin, or panitumumab.
19. Other active malignancy
20. Known alcohol abuse or drug addiction
21. Incapability to give informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
• Progression-free survival (PFS) rate at 2 years after randomisation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years after randomisation |
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E.5.2 | Secondary end point(s) |
• Treatment tolerability and side effects
• Overall survival
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• after end of chemotherapy (3 month) in both arms
• after end of maintainance (6 month) in experimental arm only
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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 | Yes |
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) | No |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
backbone chemotherapy + panitumumab compared with backbone chemotherapy only |
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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
| 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 | 70 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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
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Last follow up visit of the last subject |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |