E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Skin toxicity treatment in patients with wild-type KRAS metastatic colorectal cancer (mCRC) treated with panitumumab
• In first-line in combination with FOLFOX
• In second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan)
• As monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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 |
To compare the patient rated efficacy of preemptive basic skin treatment with or without doxycycline on the occurrence and grade of panitumumab induced skin toxicities and resulting in the end of study treatment |
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E.2.2 | Secondary objectives of the trial |
• Incidence of ≥ grade 2 skin toxicities of any type over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner
• Incidence of specific ≥ grade 2 skin toxicities over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Time to first occurrence of specific ≥ grade 2 skin toxicities - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Most severe specific ≥ grade 3 skin toxicities of interest over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Time to the first most severe specific ≥ grade 3 skin
toxicities of interest - overall and for the different treatment schemata
...FOR FURTHER SECONDARY OBJECTIVES PLEASE REFER TO PROTOCOL V 3.0 (DUE TO LIMITATION OF CHARACTERS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with wild-type KRAS metastatic colorectal cancer (mCRC) who are planned to receive treatment with panitumumab
-> In first-line in combination with FOLFOX or
-> In second-line in combination with FOLFIRI if they have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan) or
As monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens
and who did not receive any prior treatment with epidermal growth factor receptor (EGFR) antibody
2. Man or woman 18 years of age or older
3. Signed and dated informed consent before the start of specific protocol procedures
4. ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2
5. Bilirubin ≤ 1.5 x ULN, SGOT/SGPT ≤ 2.5 x ULN,
AP ≤ 3 x ULN if no evidence of liver metastases
or
Bilirubin ≤ 3 x ULN, SGOT/SGPT ≤ 5 x ULN,
AP ≤ 5 x ULN if evidence of liver metastases
6. Women of child-bearing potential have to use adaequate highly effective methods of contraception. Since doxycyline may reduce efficacy of hormonal contraceptives, women of child-bearing potential have to use double-barrier methods within 4 weeks before first intake of study medication, during study participation and at least 6 weeks after last intake of study medication even if using hormonal contraceptives Women are considered to be of child-bearing potential unless they are ≥ 50 years old and for more than 2 years amenorrhoic or unless they are surgically sterile
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E.4 | Principal exclusion criteria |
1. Absence of any of the above-listed inclusion criteria
2. Unknown KRAS or mutated KRAS of mCRC
3. Any serious medical condition or psychiatric illness that would interfere with the patient’s ability to sign the informed consent form.
4. Allergic reaction to one of the medications to be used
5. Subject allergic to panitumumab or any components of the panitumumab formulation or treatment regimen
6. Prior treatment with EGFR antibody
7. CYP3A4 enzyme inducers, inhibitors, and substrates (eg, phenytoin, phenobarbital, carbamazepine, ketoconazole, rifampicin, rifabutin, and St. John’s Wort) ≤ 2 weeks before randomization (itraconazole should be used with caution)
8. Subjects with hypersensitivity to doxycycline, other tetracyclines, or ingredients of doxycycline capsules
9. Systemic treatment with antibiotics which was completed less than 7 days prior to randomization
10. Pregnant and/or breast-feeding women
11. Active participation in other clinical studies in the previous 4 weeks
12. Serious liver function disorders
13. History of, or evidence of, interstitial pneumonitis or pulmonary fibrosis
14. Person who has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time until unblinding of skin therapy allocation (basic skin treatment with or without doxycycline) due to insufficient efficacy (i.e. unbearable skin toxicity, measured by patient’s allocating point 6 through 10 on a visual analogue scale) |
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E.5.2 | Secondary end point(s) |
• Incidence of ≥ grade 2 skin toxicities of any type over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner
• Incidence of specific ≥ grade 2 skin toxicities over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Time to first occurrence of specific ≥ grade 2 skin toxicities - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Most severe specific ≥ grade 3 skin toxicities of interest over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Time to the first most severe specific ≥ grade 3 skin toxicities - overall and for the different treatment schemata (FOLFOX + Pan, FOLFIRI +Pan, Pan mono)
• Incidence of panitumumab dose reduction due to the specific skin toxicities of interest over 12 weeks or until a value of
6-10 is observed on the VAS, whichever is sooner
• Scores in DLQI under preemptive basic skin treatment with or without doxycycline
• Type, incidence and severity of doxycycline related adverse events
• Type, incidence and severity of panitumumab related adverse events
• Response rate to panitumumab/combination of panitumumab with FOLFOX/ combination of panitumumab with FOLFIRI over 12 weeks or until a value of 6-10 is observed on the VAS, whichever is sooner (only if patient received at least 8 weeks of study treatment)
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
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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End of the study will be the last visit of the last patient having received study medication (LPLV). |
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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 | 6 |
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 |