Phase II Study of KW2871 Combined With High Dose Interferon-alpha2b in Patients With Metastatic Melanoma
Information source: Ludwig Institute for Cancer Research
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Melanoma; Cutaneous Melanoma
Intervention: Interferon alpha (Drug); KW2871 (Drug); KW2871 (Drug); interferon alpha (Drug); KW2871 (Drug); Interferon alpha (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Ludwig Institute for Cancer Research Official(s) and/or principal investigator(s): John Kirkwood, MD, Study Chair, Affiliation: University of Pittsburgh
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.
Clinical Details
Official title: Phase II Study of the Anti-Ganglioside GD3 Mouse/Human Chimeric Antibody KW2871 Combined With High Dose Interferon-alpha2b in Patients With Metastatic Melanoma
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Progression Free SurvivalToxicity
Secondary outcome: Tumor ResponseAntibody-dependent cell mediated cytotoxic (ADCC) activity and complement-dependent cytotoxic (CDC) activity Pharmacokinetic of KW2871 and the development of human antichimeric antibodies (HACA).
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University of Chicago Hospital, Chicago, Illinois 60637, United States
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, United States
Additional Information
Starting date: March 2008
Last updated: August 20, 2015
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