Recruitement did not meet expectations. Prev. differentiation of RAS-wild-type and mutated RAS are not in accordance with the scientific rank anymore.

Skin toxicity treatment in patients with advanced or metastatic colorectal cancer (mCRC) and non-mutated (wild-type) KRAS treated with panitumumab monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

Because of their frequency and severity panitumumab associated skin toxicities affect patients' quality of life and thus threaten patients' compliance to therapy. There is an urgent need for evidence-based treatment recommendations for the prevention and management of panitumumab -associated skin toxicities.

The study aims to compare the efficacy and safety of a manageable preemptive treatment with oral doxycycline in combination with a supportive topical regimen containing erythromycin cream (2 %) over duration of 12 weeks on the occurrence and grade of panitumumab induced skin toxicities in a double-blind, controlled randomized setting. Basic skin treatment with or without doxycycline will be discontinued at the end of study treatment after 12 weeks or until a value of 6-10 is observed on the visual analogue scale (VAS), whichever is sooner.

Inclusion Criteria:

1. Patients with advanced or metastatic colorectal cancer (mCRC) and non-mutated (wild-type) KRAS who are planned to receive treatment with panitumumab monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens and without 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 adequate 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 amenorrheic or unless they are surgically sterile.

Exclusion Criteria:

1. Absence of any of the above-listed inclusion criteria
2. Any serious medical condition or psychiatric illness that would interfere with the patient's ability to sign the informed consent form.
3. Allergic reaction to one of the medications to be used
4. Subject allergic to panitumumab or any components of the panitumumab formulation or treatment regimen
5. Prior treatment with EGFR antibody
6. 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)
7. Subjects with hypersensitivity to doxycycline, other tetracyclines, or ingredients of doxycycline capsules
8. Systemic treatment with antibiotics which was completed less than 7 days prior to randomization
9. Pregnant and/or breast-feeding women
10. Active participation in other clinical studies in the previous 4 weeks
11. Serious liver function disorders
12. History of, or evidence of, interstitial pneumonitis or pulmonary fibrosis
13. Person who has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.