Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: Phase II Study of KW2871 Combined With High Dose Interferon-alpha2b in Patients With Metastatic Melanoma

Summary: This study will evaluate the safety and effectiveness of the combination regimen of KW2871 and high dose Interferon-alfa2b (HDI) in patients with metastatic melanoma (skin cancer that has spread to other parts of the body).
  KW2871 is an antibody that is made in a laboratory. Antibodies are part of the immune system. KW2871 attaches to the GD3 ganglioside (a molecule that is found on melanoma cells). This may help slow or stop the growth of melanoma tumors.
  Interferon-alfa 2b is a man-made version of interferon. Interferons are among a number of substances produced by the immune system in response to the presence of enemy cells. Not only does it "interfere" with foreign invaders that may cause infection, but it can prevent the growth and spread of other diseased cells as well, including some types of cancer cells. Interferons have been shown to be effective against a variety of tumors.

Detailed description: This is an open label study of KW2871 plus high dose IFN-α2b (HDI) in patients with measurable metastatic melanoma. All eligible patients will receive KW2871 IV every two weeks (Wednesday) starting on week 1. HDI will also be given at a dose of 20 MU/m2 IV for five consecutive days (Monday thru Friday) per week for four weeks, and then 10 MU/m2 sc three times a week (Monday, Wednesday, Friday). Patients will be treated with KW2871-HDI combination therapy until disease progression requiring treatment intervention that would interfere with the interpretation of the study results.

Eligibility: Inclusion Criteria:
  1. >18 years of age
  2. Histologically proven metastatic cutaneous, mucosal, or unknown primary melanoma
  3. Measurable disease using response evaluation criteria in solid tumors RECIST criteria
  4. Are ambulatory (ECOG performance status 0 or 1) or expected survival >/= 4 months
  5. Within the last two weeks prior to study day 1, the following laboratory parameters should be within the ranges specified (Table 4):
  Table 4: Baseline peripheral laboratory values acceptable for enrollment
  -  Hemoglobin >/= 9 g/dL
  -  Platelets >/= 100 x 109/L
  -  Neutrophil count >/= 1.5 x 109/L
  -  INR </= 2.0 (</=3.0 if on warfarin therapy)
  -  Serum creatinine </=1.5 x upper limits normal
  -  Serum total bilirubin </=1.5 x upper limits normal
  -  AST(SGOT)/ALT(SGPT) </= 2.5 x upper limits normal
  6. Able and willing to give valid written informed consent
  Exclusion Criteria:
  1. Other malignancy within three years prior to study entry for which they received active treatment, except for treated melanoma or non-melanoma skin cancer and cervical and breast carcinoma in situ
  2. Mental impairment that may compromise the ability to give informed consent and comply with the study requirements
  3. Participation in any other clinical trial involving chemotherapy, radiotherapy or other immunotherapy within four weeks prior to study enrollment
  4. Prior exposure to anti-GD3 antibodies
  5. Pregnancy or breastfeeding
  6. Women of childbearing potential who refuse or are unable to use effective means of contraception
  7. Active autoimmune or other disorders that require systemic treatment with immunomodulatory or immunosuppressant medications (i.e. corticosteroids, cyclophosphamide, methotrexate, other biologics). Corticosteroids at substitution doses are allowed
  8. Metastatic brain disease is allowed provided that appropriate treatment has been administered (surgery or irradiation) and two month follow-up by brain MRI shows disease control (stability or regression)
  9. Autoimmune-related hypothyroidism and vitiligo-like depigmentation are allowed provided the patient is medically stable with treatment (thyroid-hormone replacement or observation)
  10. Serious medical illness, such as cardiovascular disease [uncontrolled congestive heart failure or hypertension, active ischemic disease of the heart (angina), recent (<3 months) myocardial infarction, severe cardiac arrhythmia], bleeding disorders, obstructive or restrictive pulmonary diseases, active systemic infections requiring antibiotics, serious intercurrent illness requiring hospitalization, inflammatory bowel disorders, or significant psychiatric disease, which in the opinion of the principal investigator would prevent adequate informed consent or render study treatment unsafe or contraindicated.
  11. Subjects with clinical suspicion of HIV or hepatitis will undergo the following viral tests:
  -  HIV (human immunodeficiency virus): subjects must have negative antibodies
  -  HBV (hepatitis B virus): subjects must have negative antigens
  -  HCV (hepatitis C virus): subjects must have a negative test for serum antibodies
  -  If any of the tests are positive patients will be excluded from the study

Relevance to patient case: not relevant