Radiation Induced Dermatitis Clinical Trial
Official title:
Randomized, Double-blind, Split-body, Placebo-controlled Phase Ib Study of APN201 (Liposomal Recombinant Human Cu/Zn-superoxide Dismutase) for the Prevention of Radiation-induced Dermatitis in Women With Breast Cancer
| Verified date | July 2013 |
| Source | Apeiron Biologics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Austria: Agency for Health and Food Safety |
| Study type | Interventional |
The standard treatment for early-stage breast cancer is breast-conserving surgery followed
by adjuvant radiation therapy to the whole breast. This approach leads to low recurrence
rates with a good cosmesis and provides an effective alternative to mastectomy. However, in
most women receiving radiotherapy radiation dermatitis occur to some degree.
Radiation dermatitis generally manifests within a few weeks after the start of radiation
therapy. Its onset varies depending on the radiation dose intensity and the normal tissue
sensitivity of individuals. As the cumulative dose of radiation increases the transient
erythema occurring during the first weeks of radiotherapy may evolve into the more
persistent erythema and to dry or even moist desquamation that reflects the damage to the
basal cell layer and the sweat and sebaceous glands.
There is currently no evidence that prophylactic treatments, beyond keeping the irradiated
area clean and dry, are effective in reducing the incidence or severity of radiation
dermatitis (Bolderston et al. 2006).
However, together with other enzymes of the peroxidase pathway, SOD scavenges the
superoxide, hydroxyl, and other oxygenated free radicals (Klug et al. 1972; Tainer at al.
1983). In physiological conditions, the production of free radicals (Monte & Sacerdote 1994)
and the action of antiradicals' enzymes is balanced. Following tissue injuries, either
pathological or caused by agents such as radiation therapy, an excess production of free
radicals is observed (Petkau 1986; Lorette & Machet 2001). Furthermore, basal SOD is
increased in breast cancer patients before radiation therapy as compared to controls (Seth
et al. 2003), and decreases after radiotherapy (Ray at al. 2000). Hence, liposomal rhSOD
applied during radiotherapy could be used to prevent the effects of free radicals and thus
might protect the patient's skin from radiation-induced skin reactions.
TREATMENT PLAN All patients receive APN201 and placebo at the same time. The irradiated
region is divided vertically into two symmetric areas (left and right). One area is treated
with APN201, the other area is treated with placebo in a double-blind fashion.
Study treatment (APN201 and placebo) starts on the day of initiation of radiation therapy
and continues until the end of radiation therapy to the whole breast (25 or 28 daily
fractions to a total dose of 50.0 Gy or 50.4 Gy, respectively) (see schedule of assessments,
section 5.1).
Study treatment is stopped if radiation dermatitis of ≥ grade 2 occurs in one or both
treated areas for ≥ 3 days AND a difference in the severity of radiation dermatitis of ≥ 1
grade is seen between the two treated areas. From that point in time the patient only
receives the treatment that appeared to be beneficial and this treatment is applied to the
whole irradiated region until completion of the 25th, respectively 28th, fraction.
Treatment stops earlier in case of progressive disease or unacceptable toxicity or
intolerability.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | May 2012 |
| Est. primary completion date | May 2012 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Women = 18 years of age, with breast cancer, treated by breast conserving surgery and scheduled to receive adjuvant radiotherapy to the breast alone - Bra cup size =D - Karnofsky performance status of = 80% - Women of childbearing potential must have a negative pregnancy test before study entry and must agree to use a medically acceptable method of birth control throughout the study period - Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: - Bilateral breast cancer - Inflammatory breast cancer - Lymphangiosis carcinomatosa - Medically significant dermatologic conditions affecting the irradiated area - Planned use of other agents with the aim of preventing and/or treating radiation dermatitis - Concomitant medications which might exacerbate radiation dermatitis - History of previous radiation therapy of the breast - Pregnancy or breastfeeding - Having received any other investigational agent within 4 weeks before enrolment - Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| Austria | Medical University Graz; Department of Therapeutic Radiology and Oncology | Graz |
| Lead Sponsor | Collaborator |
|---|---|
| Apeiron Biologics |
Austria,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To evaluate safety and tolerability of APN201 | Adverse events, vital signs and laboratory assessments (hematology, serum chemistry) are used for safety evaluations. | From baseline until 1 day following the final radiotherapy fraction, assessed for a maximum of 28 radiotherapy fractions. | Yes |
| Secondary | To evaluate the efficacy of APN201 in the prevention of radiation-induced dermatitis | The following parameters are used for efficacy evaluations: Time to = grade 2 radiation dermatitis Incidence of = grade 2 radiation dermatitis Severity of radiation dermatitis Pain intensity (pain on touching the skin) due to radiation therapy Irradiated skin evaluations using the digital wound documentation system W.H.A.T. (wound healing analysing tool) and a spectrophotometer |
From baseline until 1 day after the final radiotherapy fraction, assessed for a maximum of 28 radiotherapy fractions. | No |