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

This study is currently recruiting participants.
Verified April 2012 by Ludwig Institute for Cancer Research
Sponsor:
Collaborator:
Life Sciences Pharmaceuticals
Information provided by:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00679289
First received: May 14, 2008
Last updated: April 16, 2012
Last verified: April 2012
History of Changes
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma
U.S. FDA Resources

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

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: ongoing ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Ongoing until disease progression ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor Response [ Time Frame: Ongoing until disease progression ] [ Designated as safety issue: No ]
  • Antibody-dependent cell mediated cytotoxic (ADCC) activity and complement-dependent cytotoxic (CDC) activity [ Time Frame: Ongoing until disease progression ] [ Designated as safety issue: No ]
  • Pharmacokinetic of KW2871 and the development of human antichimeric antibodies (HACA). [ Time Frame: Ongoing until disease progression ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: March 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

KW2871 (5 mg/m2) IV Q2W until disease progression

Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression

 Drug: Interferon alpha
20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression
Other Name: Intron A
Drug: KW2871
5 mg/m2 IV Q2W until disease progression
Other Name: Ecromeximab
Experimental: 2

KW2871 10 mg/m2 IV Q2W until disease progression

Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression

 Drug: KW2871
10 mg/m2 IV Q2W until disease progression
Other Name: Ecromeximab
Drug: interferon alpha
20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression
Other Name: Intron A
Experimental: 3

KW2871 20 mg/m2 IV Q2W until disease progression

Interferon alpha 20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression

 Drug: KW2871
20 mg/m2 IV Q2W until disease progression
Other Name: Ecromeximab
Drug: Interferon alpha
20 MU/m2 IV QD x 5 Days for 4 weeks, then 10 MU/m2 SC TIW until disease progression
Other Name: Intron A

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: William Trost     773-702-2085     wtrost@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: Ping DeBlasio, RN     412-623-7957     DeBlasioWX@upmc.edu    
Sub-Investigator: John Kirkwood, MD            
Principal Investigator: Stergios Moschos, MD            
Sub-Investigator: Ahmad Tahrini, MD            
Sub-Investigator: Howard Edington, MD            
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

No publications provided

Responsible Party: Ralph Venhaus, Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00679289     History of Changes
Other Study ID Numbers: LUD2007-001, UPCI07-023, UCH15689B
Study First Received: May 14, 2008
Last Updated: April 16, 2012
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

Additional relevant MeSH terms:
Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
 Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Adjuvants, Immunologic
Alcohol Deterrents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 21, 2013