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

Colorectal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01418742
• Other study ID #: GMIHO-010/2009
• Status: Terminated
• Phase: Phase 2
• First received: August 3, 2011
• Last updated: July 11, 2014
• Start date: August 2011
• Est. completion date: May 2013

Study information

• Verified date: March 2013
• Source: Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• Panitumumab, Doxycycline/Placebo
comparison of Doxycyline/Placebo and Panitumumab regarding efficacy of the therapy of panitumumab induced skin toxicity
• Panitumumab
mCRC patients receiving panitumumab as EGFR inhibitor.

Locations

Country	Name	City	State
Germany	Charité Campus Virchow Klinikum (CVK), Centrum für Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie u. Onkologie	Berlin
Germany	DRK Kliniken Berlin / Köpenick, Klinik für Chirurgie	Berlin
Germany	Medizinisches Versorgungszentrum Ärzteforum Seestraße	Berlin
Germany	Onkologische Schwerpunktpraxis	Berlin
Germany	Ärzteforum Bernau	Bernau
Germany	Onkologische Schwerpunktpraxis	Brandenburg
Germany	Städtisches Klinikum Dessau, Hömatologie und Internistische Onkologie	Dessau
Germany	St. Georg Klinikum Eisenach gGmbH, Klinik für Innere Medizin 2	Eisenach
Germany	Krankenhaus St. Elisabeth u. St. Barbara, Klinik für Allgemein- u. Visceralchirurgie	Halle
Germany	Ärzteforum Hennigsdorf	Hennigsdorf
Germany	eps-early phase GmbH	Jena
Germany	Klinikum Dorothea Christiane Erxleben Quedlinburg gGmbH, Klinik f. Allgemein, Vizeral- und Gefäßchirurgie	Quedlinburg

Sponsors (2)

Lead Sponsor	Collaborator
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH	ClinAssess GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	Time to first occurrence of specific = grade 2 skin toxicities		30 months	Yes
Secondary	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	Yes
Secondary	Time to the first most severe specific = grade 3 skin toxicities		30 month	Yes
Secondary	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	Yes
Secondary	Scores in DLQI under preemptive basic skin treatment with or without doxycycline		30month	Yes
Secondary	Incidence of doxycycline related adverse events		30 month	Yes
Secondary	Type of panitumumab related adverse events		30 month	Yes
Secondary	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	Yes
Secondary	Type of doxycycline related adverse events		30 month	Yes
Secondary	Severity of doxycycline related adverse events		30 month	Yes
Secondary	Incidence of panitumumab related adverse events		30 month	Yes
Secondary	Severity of panitumumab related adverse events		30 month	Yes