A Randomized, Open-label Phase III Trial of Mapisal® Versus an Urea Hand-foot Cream as Prophylaxis for Capecitabine-induced Hand-foot Syndrome in Patients With Gastrointestinal Tumors or Breast Cancer

The purpose of this study is the examination of Mapisal® versus urea hand-foot cream as prophylaxis for capecitabine-induced hand-foot syndrome (HFS) in patients with gastrointestinal tumors or breast cancer, to assess the efficacy of Mapisal®.

Mapisal® is a medical device that is approved for the prophylaxis and treatment of HFS. Initial clinical data and case studies on the treatment and prophylaxis of Caelyx-induced HFS have been impressive. Because the pathomechanism of HFS caused by capecitabine is the same as for Caelyx-induced HFS, it is expected reason that administering Mapisal® should result in a significant reduction of HFS caused by capecitabine. The urea hand-foot cream was selected for the standard arm, because it is used commonly, is accepted by patients, and seems to have a positive influence on the severity of the HFS in the experience of many oncologists.

Hand-foot syndrome (HFS) is a frequently occurring, often dose limiting, dermatologic reaction associated with cytotoxic agents, such as capecitabine, liposomal doxorubicin, and doxetacel.

Adverse events affecting the integument have posed significant challenges to oncologists in recent years in terms of selecting appropriate supportive therapies. Not only medications that inhibit EGFR receptors such as erlotinib, gefitinib, panitumumab or cetuximab, but also multiple-receptor tyrosine kinase inhibitors such as sunitinib and sorafenib and other "older" medications such as capecitabine can often lead to skin-related adverse events that can be difficult to manage.

These adverse events compromise skin-related quality of life and can lead to dose compromises or even the termination of treatment.

To date, there are no side effects reported for the use of either Mapisal® or urea hand-foot cream, making both treatments safe. Given the potential benefits of the treatments in preventing HFS by reducing discomfort and impairment of quality of life, the conduct of the trial is regarded as justifiable and there is no indication that patients are exposed to an increased risk associated with study participation.

Eligibility Criteria:
Inclusion Criteria:

1. Signed written informed consent
2. Male or female ≥18 years of age
3. Patients with gastrointestinal tumors or breast cancer who will be treated with capecitabine according to label
4. Palliative or adjuvant chemotherapy with capecitabine (combination- or mono-therapy, minimal dose of capecitabine 2000 mg/m2)
5. Life expectancy of least 12 weeks
6. WHO performance status 0-2
7. Adequate contraception
8. Willingness to fill in QoL forms
9. Laboratory requirements

   * Platelet count ≥100 × 109/L
   * Leukocyte count \> 3.0 × 109/L
   * Hemoglobin ≥ 10.0 g/dL
10. Resolution of all chemotherapy- or radiotherapy-related toxicities to grade 1 or lower except for stable sensory neuropathy \< grade 2. Any dermatological toxicities other than alopecia resulting from previous chemotherapy or radiotherapy must be completely resolved.

Exclusion Criteria:

1. Previous chemotherapy with capecitabine or liposomal doxorubicine, or any other substance, i.e. tyrosine kinase inhibitors (such as sorafenib and sunitinib) that may induce HFS
2. Radiotherapy or surgery within 4 weeks before start of treatment.
3. Dermatologic diseases that could interfere with the result of the clinical trial
4. Known drug/ alcohol abuse
5. Pregnant or breast feeding patients
6. Participation in another clinical trial and patient received investigational drug within the last 30 days prior to treatment start (i.e. follow-up within a preceding trial is not exclusionary)
7. Known allergic reactions to any of the ingredients of the ointments or capecitabine