SKIP - A Double-blind Placebo-controlled Randomized Multicenter Trial of Skin Toxicity Treatment

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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SKIP - A Double-blind Placebo-controlled Randomized Multicenter Phase II Trial of Skin Toxicity Treatment in Subjects With Advanced or Metastatic Colorectal Carcinoma Receiving Panitumumab

Conditions
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Colorectal Carcinoma

Intervention / Treatment
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* Drug: Panitumumab, Doxycycline/Placebo
* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Man or woman 18 years of age or older Signed and dated informed consent before the start of specific protocol procedures ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 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 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: Absence of any of the above-listed inclusion criteria Any serious medical condition or psychiatric illness that would interfere with the patient's ability to sign the informed consent form. Allergic reaction to one of the medications to be used Subject allergic to panitumumab or any components of the panitumumab formulation or treatment regimen Prior treatment with EGFR antibody 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) Subjects with hypersensitivity to doxycycline, other tetracyclines, or ingredients of doxycycline capsules Systemic treatment with antibiotics which was completed less than 7 days prior to randomization Pregnant and/or breast-feeding women Active participation in other clinical studies in the previous 4 weeks Serious liver function disorders History of, or evidence of, interstitial pneumonitis or pulmonary fibrosis Person who has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Doxycycline 100 mg BID oral use<br> | Drug: Panitumumab, Doxycycline/Placebo<br>* comparison of Doxycyline/Placebo and Panitumumab regarding efficacy of the therapy of panitumumab induced skin toxicity<br>|
| Placebo Comparator: Placebo 100 mg BID oral use<br> | Drug: Panitumumab<br>* mCRC patients receiving panitumumab as EGFR inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | 30 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 30 months | 
| Time to first occurrence of specific ≥ grade 2 skin toxicities |  | 30 months | 
| 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 |  | 30 months | 
| Time to the first most severe specific ≥ grade 3 skin toxicities |  | 30 month | 
| 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 |  | 30 month | 
| Scores in DLQI under preemptive basic skin treatment with or without doxycycline |  | 30month | 
| Incidence of doxycycline related adverse events |  | 30 month | 
| Type of panitumumab related adverse events |  | 30 month | 
| Response rate to panitumumab 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) |  | 30 month | 
| Type of doxycycline related adverse events |  | 30 month | 
| Severity of doxycycline related adverse events |  | 30 month | 
| Incidence of panitumumab related adverse events |  | 30 month | 
| Severity of panitumumab related adverse events |  | 30 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin toxicity