Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of QoL in Patient With Ras-wt Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AIO-Studien-gGmbH
Sponsor:
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT01668498
First received: August 16, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

80 - 90 % of the patients treated with anti-EGFR antibodies (panitumumab or cetuximab) experience skin toxicity, mostly acne like skin rash.

A standardized treatment of skin rash is neither established as standard arm for clinical trials nor as guideline for the treatment of skin toxicity in clinical practice. While an improvement of QoL has been demonstrated for panitumumab and cetuximab in comparison to best supportive care the data basis for patient related outcomes regarding skin toxicity deriving from randomized trials is still small.

Recent surveys among German oncologist revealed that physicians are reluctant to use oral antibiotics as preemptive treatment . Only 19 out of 110 oncologists stated that they are thinking about using preemptive treatment in patients with acne-like skin rash.

Thus, in the present trial two main questions will be addressed:

(i) Can preemptive treatment with oral doxycycline be replaced by a sequential skin treatment strategy (i.e. local treatment with erythromycin followed by doxycycline in case of inefficacy = development of acne) without compromising treatment efficacy of skin toxicity treatment? (ii) Comparison of general and skin related QoL between both treatment arms.


Condition Intervention Phase
Ras-wildtype Colorectal Cancer
Drug: Erythromycin
Drug: Doxycycline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of Quality of Life in Patients With Ras-wildtype Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • Percentage of patients developing no skin toxicity ≥ grade 2 [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.


Secondary Outcome Measures:
  • Quality of life [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    Quality of life will be assessed by standardized skin-related (DLQI) and global quality of life (EORTC QLQ C30.

    For correlation analyses between the different quality of life scores, the non-parametric test according to Spearman will preferably be applied.


  • Assess Skin toxicity [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Assess different skin toxicity grading scales (i.e. NCI CTC v. 4.0; WoMo score; MESTT)

  • Correlation between skin-related and global quality of life [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.

  • late skin toxicity [ Time Frame: from week 8 to 12 ] [ Designated as safety issue: Yes ]
    Describe the development of late skin toxicity after 8 weeks

  • Skin-toxicity related dose reductions of panitumumab [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab


Estimated Enrollment: 74
Study Start Date: May 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erythromycin
Experimental Arm (ARM A) skin- treatment: erythromycin cream 2% daily at bedtime doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2 skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
Drug: Erythromycin
Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.
Other Name: Aknemycin
Active Comparator: Doxycyline
Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
Drug: Doxycycline
Comparison of efficacy of Arm A erythromycin cream 2% daily at bedtime (doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2) and Arm B doxycycline 100mg b.i.d. in patients with Metastatic Colorectal cancer (Ras wild-type)being treated with panitumumab.

  Eligibility

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

Inclusion Criteria:

  1. Patients with wild-type RAS (KRAS and NRAS) status of metastatic colorectal cancer treatment with panitumumab according to label

    • RAS wild-type tested in
    • KRAS exon 2 (codons 12/13)
    • KRAS exon 3 (codons 59/61)
    • KRAS exon 4 (codons 117/146)
    • NRAS exon 2 (codons 12/13)
    • NRAS exon 3 (codons 59/61)
    • NRAS exon 4 (codons 117/146)
  2. treatment with pre-emptive study medication shall begin the day before treatment start with panitumumab
  3. Willingness to cope with biweekly quality of life questionnaires
  4. Written Informed consent
  5. Aged at least 18 years
  6. ECOG Performance Status 0-2
  7. Life expectancy of at least 12 weeks
  8. Adequate haematological, hepatic, renal and metabolic function parameters:

    • Leukocytes > 3000/mm³
    • ANC ≥ 1500/mm³
    • Platelets ≥ 100,000/mm³
    • Haemoglobin > 9 g/dl
    • Serum creatinine ≤ 1.5 x ULN
    • Bilirubin ≤ 1.5 x ULN
    • GOT-GPT ≤ 2.5 x ULN (in case of liver metastases GOT / GPT ≤ 5 x ULN)
    • AP ≤ 5 x ULN
    • Magnesium, Calcium and potassium within normal ranges (may be substituted before study entry)

Exclusion criteria:

  1. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
  2. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
  3. Serious concurrent diseases
  4. On-treatment participation in a clinical study in the period 30 days prior to inclusion
  5. Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
  6. History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
  7. History of HIV infection.
  8. Other previous or concurrent malignancy (≤ 5 years prior to enrolment in study) except non-melanoma skin cancer or cervical carcinoma FIGO stage 0- 1 if the patient is continuously disease-free
  9. Known allergic reactions on panitumumab, doxycycline or erythromycin
  10. Previous treatment with anti-cancer agents directed against EGFR (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib)
  11. Skin rash existing before or due to other reasons than panitumumab treatment
  12. Other dermatologic disease that may interfere with correct grading of panitumumab induced skin rash
  13. Parallel treatment with anti-tumor agents other than panitumumab
  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: NCT01668498

Contacts
Contact: Karin Krause, B.Sc. Katrin.Krause@aio-studien-ggmbh.de

Locations
Germany
Universitätsklinikum Mannheim, III. Medizinische Klinik Recruiting
Mannheim, Germany, 68167
Contact: Melanie Kripp, Dr.    +49621383 ext 2855    melanie.kripp@umm.de   
Sponsors and Collaborators
AIO-Studien-gGmbH
Investigators
Principal Investigator: Melanie Kripp, Dr. med. III. Medizinische Klinik, Universitätsmedizin Mannheim
  More Information

Additional Information:
No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT01668498     History of Changes
Other Study ID Numbers: AIO-LQ-0110, 2010-022938-85
Study First Received: August 16, 2012
Last Updated: July 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by AIO-Studien-gGmbH:
Can preemptive treatment of panitumumab mediated skin
toxicity with oral doxycycline be replaced by local treatment with erythromycin?
Panitumumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Doxycycline
Erythromycin
Erythromycin Estolate
Erythromycin Ethylsuccinate
Erythromycin stearate
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Gastrointestinal Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014