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

Primary Purpose

Ras-wildtype Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Erythromycin

Doxycycline

About this trial

This is an interventional prevention trial for Ras-wildtype Colorectal Cancer focused on measuring Can preemptive treatment of panitumumab mediated skin, toxicity with oral doxycycline be replaced by local treatment with erythromycin?, Panitumumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
treatment with pre-emptive study medication shall begin the day before treatment start with panitumumab
Willingness to cope with biweekly quality of life questionnaires
Written Informed consent
Aged at least 18 years
ECOG Performance Status 0-2
Life expectancy of at least 12 weeks
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:

Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
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).
Serious concurrent diseases
On-treatment participation in a clinical study in the period 30 days prior to inclusion
Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
History of HIV infection.
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
Known allergic reactions on panitumumab, doxycycline or erythromycin
Previous treatment with anti-cancer agents directed against EGFR (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib)
Skin rash existing before or due to other reasons than panitumumab treatment
Other dermatologic disease that may interfere with correct grading of panitumumab induced skin rash
Parallel treatment with anti-tumor agents other than panitumumab

Sites / Locations

Universitätsklinikum Mannheim, III. Medizinische Klinik

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Erythromycin

Doxycyline

Arm Description

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

Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks

Outcomes

Primary Outcome Measures

Percentage of patients developing no skin toxicity ≥ grade 2

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

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

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

Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.

late skin toxicity

Describe the development of late skin toxicity after 8 weeks

Skin-toxicity related dose reductions of panitumumab

Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab

Full Information

NCT ID

NCT01668498

First Posted

August 16, 2012

Last Updated

April 18, 2016

Sponsor

AIO-Studien-gGmbH

1. Study Identification

Unique Protocol Identification Number

NCT01668498

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

May 2011 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AIO-Studien-gGmbH

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ras-wildtype Colorectal Cancer

Keywords

Can preemptive treatment of panitumumab mediated skin, toxicity with oral doxycycline be replaced by local treatment with erythromycin?, Panitumumab

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

88 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erythromycin

Arm Type

Experimental

Arm Description

Arm Title

Doxycyline

Arm Type

Active Comparator

Arm Description

Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks

Intervention Type

Drug

Intervention Name(s)

Erythromycin

Other Intervention Name(s)

Aknemycin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Doxycycline

Intervention Description

Primary Outcome Measure Information:

Title

Percentage of patients developing no skin toxicity ≥ grade 2

Description

Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Quality of life

Description

Time Frame

8 weeks

Title

Assess Skin toxicity

Description

Assess different skin toxicity grading scales (i.e. NCI CTC v. 4.0; WoMo score; MESTT)

Time Frame

8 weeks

Title

Correlation between skin-related and global quality of life

Description

Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.

Time Frame

8 weeks

Title

late skin toxicity

Description

Describe the development of late skin toxicity after 8 weeks

Time Frame

from week 8 to 12

Title

Skin-toxicity related dose reductions of panitumumab

Description

Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) treatment with pre-emptive study medication shall begin the day before treatment start with panitumumab Willingness to cope with biweekly quality of life questionnaires Written Informed consent Aged at least 18 years ECOG Performance Status 0-2 Life expectancy of at least 12 weeks 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: Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. 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). Serious concurrent diseases On-treatment participation in a clinical study in the period 30 days prior to inclusion Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment. History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. History of HIV infection. 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 Known allergic reactions on panitumumab, doxycycline or erythromycin Previous treatment with anti-cancer agents directed against EGFR (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) Skin rash existing before or due to other reasons than panitumumab treatment Other dermatologic disease that may interfere with correct grading of panitumumab induced skin rash Parallel treatment with anti-tumor agents other than panitumumab

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melanie Kripp, Dr. med.

Organizational Affiliation

III. Medizinische Klinik, Universitätsmedizin Mannheim

Official's Role

Principal Investigator

Facility Information:

Facility Name

Universitätsklinikum Mannheim, III. Medizinische Klinik

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

12. IPD Sharing Statement

Links:

URL

http://www.aio-portal.de

Description

Related Info

Learn more about this trial

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

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