Phase II Study of KW2871 Combined With High Dose Interferon-alpha2b in Patients With Metastatic Cutaneous Melanoma - Full Text View

Sponsors and Collaborators:	Ludwig Institute for Cancer Research Life Sciences Pharmaceuticals
Information provided by:	Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:	NCT00679289

Purpose

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.

Condition	Intervention	Phase
Metastatic Melanoma Cutaneous Melanoma	Drug: Interferon alpha Drug: KW2871 Drug: interferon alpha	Phase II

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Immunoglobulins Globulin, Immune Interferon alfa-n1 Interferon alfa-2a Interferon alfa-2b Interferons

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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 Cutaneous Melanoma

Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:

Progression Free Survival [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
Toxicity [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tumor Response [ Time Frame: Within 14 weeks ] [ Designated as safety issue: No ]
Antibody-dependent cell mediated cytotoxic (ADCC) activity and complement-dependent cytotoxic (CDC) activity [ Time Frame: 14 wks ] [ Designated as safety issue: No ]
Pharmacokinetic of KW2871 and the development of human antichimeric antibodies (HACA). [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	March 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental KW2871 (5 mg/m2) IV Q2W for 14 weeks Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks	Drug: Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks Drug: KW2871 5 mg/m2 IV Q2W for 14 weeks
2: Experimental KW2871 10 mg/m2 IV Q2W for 14 weeks Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks	Drug: KW2871 10 mg/m2 IV Q2W for 14 weeks Drug: interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks
3: Experimental KW2871 20 mg/m2 IV Q2W for 14 weeks Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks	Drug: KW2871 20 mg/m2 IV Q2W for 14 weeks Drug: Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW for 10 weeks

Detailed Description:

This is an open-label study of KW2871 plus high dose IFN-α2b (HDI) for patients with measurable metastatic melanoma. Eligible patients will receive up to fourteen weeks of the KW2871-HDI combination therapy: the regimen consists of KW2871 administered intravenously (IV) every two weeks (Wednesdays) for seven infusions, plus HDI at a dose of 20 million units (MU)/m2 administered IV for five consecutive days per week (Monday thru Friday) for the first four weeks, and then 10 MU/m2 SC thrice weekly (Monday, Wednesday, Friday) for ten weeks for a total treatment period of fourteen weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

>18 years of age
Histologically proven metastatic cutaneous melanoma
Measurable disease using response evaluation criteria in solid tumors RECIST criteria
Are ambulatory (ECOG performance status 0 or 1) or expected survival >/= 4 months
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
Able and willing to give valid written informed consent

Exclusion Criteria:

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
Mental impairment that may compromise the ability to give informed consent and comply with the study requirements
Participation in any other clinical trial involving chemotherapy, radiotherapy or other immunotherapy within four weeks prior to study enrollment
Prior exposure to anti-GD3 antibodies
Pregnancy or breastfeeding
Women of childbearing potential who refuse or are unable to use effective means of contraception
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
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)
Autoimmune-related hypothyroidism and vitiligo-like depigmentation are allowed provided the patient is medically stable with treatment (thyroid-hormone replacement or observation)
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.
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679289

Locations

United States, Illinois
University of Chicago Hospital	Recruiting
Chicago, Illinois, United States, 60637
Contact: Corinne Ball, B.S. 773-834-2643 cball1@medicine.bsd.uchicago.edu
Principal Investigator: Thomas Gajewski, MD, PhD
Sub-Investigator: Walter Stadler, MD, FACP
United States, Pennsylvania
University of Pittsburgh Cancer Institute	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Amy Rose, RN roseaj2@upmc.edu
Principal Investigator: John Kirkwood, MD
Sub-Investigator: Stergios Moschos, MD
Sub-Investigator: Ahmad Tahrini, MD
Sub-Investigator: Howard Edington, MD
Sub-Investigator: Charles Brown, MD, PhD
Sub-Investigator: Hussein Tawbi, MD
Sub-Investigator: Hassane Zarour, MD
Sub-Investigator: Janice Shipe-Spotloe, MA, PA-C
Sub-Investigator: Melissa Demark, MA, PA-C

Sponsors and Collaborators

Ludwig Institute for Cancer Research

Life Sciences Pharmaceuticals

Investigators

Study Chair:

John Kirkwood, MD

University of Pittsburgh

More Information

Responsible Party:	Ludwig Institute for Cancer Research ( Ralph Venhaus )
Study ID Numbers:	LUD2007-001, UPCI07-023, UCH15689B
Study First Received:	May 14, 2008
Last Updated:	May 14, 2008
ClinicalTrials.gov Identifier:	NCT00679289
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ludwig Institute for Cancer Research:

KW2871
ecromeximab
anti-ganglioside

antibody
interferon alpha
Metastatic melanoma

Study placed in the following topic categories:

Interferon-alpha
Interferon Type I, Recombinant
Interferons
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Antibodies
Neoplasms, Germ Cell and Embryonal

Nevus, Pigmented
Melanoma, familial
Neuroepithelioma
Nevus
Interferon Alfa-2a
Interferon Alfa-2b
Immunoglobulins

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms by Histologic Type
Immunologic Factors
Antineoplastic Agents
Growth Substances
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Antiviral Agents

Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Nevi and Melanomas
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 15, 2009