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

This study has been terminated.
(Recruitement did not meet expectations. Prev. differentiation of RAS-wild-type and mutated RAS are not in accordance with the scientific rank anymore.)
Sponsor:
Collaborator:
ClinAssess GmbH
Information provided by (Responsible Party):
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier:
NCT01418742
First received: August 3, 2011
Last updated: July 11, 2014
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Carcinoma
Drug: Panitumumab, Doxycycline/Placebo
Drug: Panitumumab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH:

Primary Outcome Measures:
  • 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) [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • Time to first occurrence of specific ≥ grade 2 skin toxicities [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • Time to the first most severe specific ≥ grade 3 skin toxicities [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Scores in DLQI under preemptive basic skin treatment with or without doxycycline [ Time Frame: 30month ] [ Designated as safety issue: Yes ]
  • Incidence of doxycycline related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Type of panitumumab related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Type of doxycycline related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Severity of doxycycline related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Incidence of panitumumab related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]
  • Severity of panitumumab related adverse events [ Time Frame: 30 month ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: August 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01418742

Locations
Germany
Charité Campus Virchow Klinikum (CVK), Centrum für Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie u. Onkologie
Berlin, Germany, 13355
DRK Kliniken Berlin / Köpenick, Klinik für Chirurgie
Berlin, Germany, 12559
Medizinisches Versorgungszentrum Ärzteforum Seestraße
Berlin, Germany, 13347
Onkologische Schwerpunktpraxis
Berlin, Germany, 13055
Ärzteforum Bernau
Bernau, Germany, 16321
Onkologische Schwerpunktpraxis
Brandenburg, Germany, 14770
Städtisches Klinikum Dessau, Hömatologie und Internistische Onkologie
Dessau, Germany, 06847
St. Georg Klinikum Eisenach gGmbH, Klinik für Innere Medizin 2
Eisenach, Germany, 99817
Krankenhaus St. Elisabeth u. St. Barbara, Klinik für Allgemein- u. Visceralchirurgie
Halle, Germany, 06110
Ärzteforum Hennigsdorf
Hennigsdorf, Germany, 16761
eps-early phase GmbH
Jena, Germany, 07743
Klinikum Dorothea Christiane Erxleben Quedlinburg gGmbH, Klinik f. Allgemein, Vizeral- und Gefäßchirurgie
Quedlinburg, Germany, 06484
Sponsors and Collaborators
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinAssess GmbH
Investigators
Study Chair: Hanno Riess, Prof. Charité Campus Virchow Klinikum, Klinik für Innere Medizin mit Schwerpunkt Hämatologie u. Onkologie
  More Information

No publications provided

Responsible Party: Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier: NCT01418742     History of Changes
Other Study ID Numbers: GMIHO-010/2009
Study First Received: August 3, 2011
Last Updated: July 11, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH:
skin toxicity

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Antibodies, Monoclonal
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014