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

Sponsor

AIO-Studien-gGmbH (Other)

Overall Status

Completed

CT.gov ID

NCT01668498

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Ras-wildtype Colorectal Cancer	Drug: Erythromycin Drug: Doxycycline	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

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	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 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	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.

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

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 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

Drug: Doxycycline

Outcome Measures

Primary Outcome Measures

Percentage of patients developing no skin toxicity ≥ grade 2 [8 weeks]
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 [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.
Assess Skin toxicity [8 weeks]
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 [8 weeks]
Description of correlation between skin-related and global quality of life using EORTC-QLQ C30 and SF-36.
late skin toxicity [from week 8 to 12]
Describe the development of late skin toxicity after 8 weeks
Skin-toxicity related dose reductions of panitumumab [8 weeks]
Rate of skin-toxicity induced dose reductions (including withdrawal) of panitumumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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