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

April 18, 2016 updated by: AIO-Studien-gGmbH

Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of Quality of Life in Patients With Ras-wildtype Colorectal Cancer

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.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Mannheim, Germany, 68167
        • Universitätsklinikum Mannheim, III. Medizinische Klinik

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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 Names:
  • 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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients developing no skin toxicity ≥ grade 2
Time Frame: 8 weeks
Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life
Time Frame: 8 weeks

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.

8 weeks
Assess Skin toxicity
Time Frame: 8 weeks
Assess different skin toxicity grading scales (i.e. NCI CTC v. 4.0; WoMo score; MESTT)
8 weeks
Correlation between skin-related and global quality of life
Time Frame: 8 weeks
Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.
8 weeks
late skin toxicity
Time Frame: from week 8 to 12
Describe the development of late skin toxicity after 8 weeks
from week 8 to 12
Skin-toxicity related dose reductions of panitumumab
Time Frame: 8 weeks
Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Melanie Kripp, Dr. med., III. Medizinische Klinik, Universitätsmedizin Mannheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

August 16, 2012

First Submitted That Met QC Criteria

August 17, 2012

First Posted (Estimate)

August 20, 2012

Study Record Updates

Last Update Posted (Estimate)

April 19, 2016

Last Update Submitted That Met QC Criteria

April 18, 2016

Last Verified

April 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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