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 MedDRA version: 16.0 Level: PT Classification code 10052358 Term: Colorect
Conditions
Interventions
Trade Name: Vectibix
Product Name: Vectibix
Product Code: Vectibix
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PANITUMUMAB
CAS Number: 339177-26-3
Current Sponsor c
Sponsors
GMIHO Gesellschaft für Medizinische Innovation – Hämatologie und Onkologie mbH
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • 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) ;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);Main Objective: 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Germany
Contacts
Public ContactGMIHO mbH
GMIHO Gesellschaft für Medizinische Innovation – Hämatologie und Onkologie mbH
Outcome results
None listed