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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Carcinoma
• Intervention / Treatment: Drug: Panitumumab, Doxycycline/Placebo; Drug: Panitumumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12559
    • DRK Kliniken Berlin / Köpenick, Klinik für Chirurgie
  • Berlin, Germany, 13055
    • Onkologische Schwerpunktpraxis
  • Berlin, Germany, 13347
    • Medizinisches Versorgungszentrum Ärzteforum Seestraße
  • Berlin, Germany, 13355
    • Charité Campus Virchow Klinikum (CVK), Centrum für Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie u. Onkologie
  • Bernau, Germany, 16321
    • Ärzteforum Bernau
  • Brandenburg, Germany, 14770
    • Onkologische Schwerpunktpraxis
  • Dessau, Germany, 06847
    • Städtisches Klinikum Dessau, Hömatologie und Internistische Onkologie
  • Eisenach, Germany, 99817
    • St. Georg Klinikum Eisenach gGmbH, Klinik für Innere Medizin 2
  • Halle, Germany, 06110
    • Krankenhaus St. Elisabeth u. St. Barbara, Klinik für Allgemein- u. Visceralchirurgie
  • Hennigsdorf, Germany, 16761
    • Ärzteforum Hennigsdorf
  • Jena, Germany, 07743
    • eps-early phase GmbH
  • Quedlinburg, Germany, 06484
    • Klinikum Dorothea Christiane Erxleben Quedlinburg gGmbH, Klinik f. Allgemein, Vizeral- und Gefäßchirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Doxycycline 100 mg BID oral use	Drug: Panitumumab, Doxycycline/Placebo; comparison of Doxycyline/Placebo and Panitumumab regarding efficacy of the therapy of panitumumab induced skin toxicity
PLACEBO_COMPARATOR: Placebo 100 mg BID oral use	Drug: Panitumumab; mCRC patients receiving panitumumab as EGFR inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
• Collaborators: ClinAssess GmbH
• Investigators: Study Chair: Hanno Riess, Prof., Charité Campus Virchow Klinikum, Klinik für Innere Medizin mit Schwerpunkt Hämatologie u. Onkologie

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): May 1, 2013

Study Registration Dates

• First Submitted: August 3, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (ESTIMATE): August 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: skin toxicity
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Anti-Infective Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Panitumumab
• Other Study ID Numbers: GMIHO-010/2009