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Study of Denileukin Diftitox in Patients With Stage IIIC and Stage IV Melanoma

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified March 2015 by Eisai Inc..
Recruitment status was:  Active, not recruiting
PharmaBio Development Inc.
Information provided by (Responsible Party):
Eisai Inc. Identifier:
First received: May 19, 2010
Last updated: March 31, 2015
Last verified: March 2015
The purpose of this study is to determine whether Patients with Stage IIIC and Stage IV Melanoma experience benefit when treated with Denileukin diftitox in two different dosing schedules.

Condition Intervention Phase
Stage IIIC Melanoma
Stage IV Melanoma
Drug: Denileukin diftitox
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open-Label, Multicenter Study of Denileukin Diftitox in Patients With Stage IIIC and Stage IV Melanoma

Resource links provided by NLM:

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Safety Parameter [ Time Frame: AEs and conmeds - until study termination; lab tests Day 1 and every 21 days until study termination ]
    Safety parameters: adverse events (AEs); vital signs; clinical laboratory evaluations; and physical examinations

Secondary Outcome Measures:
  • Efficacy Parameter [ Time Frame: on Day 84 and every 3 months thereafter, for up to 1 year after the last treatment administration or until disease progression ]

    Progression-free survival (PFS),

    • Response duration
    • Overall survival

Estimated Enrollment: 90
Study Start Date: June 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denileukin diftitox
12 mcg/kg/day on Days 1 through 4 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks)
Drug: Denileukin diftitox

Test product: dose and mode of administration:

denileukin diftitox was originally administered by intravenous infusion over 30-60 minutes according to 1 of 2 treatment arms:

  1. 12 mcg/kg/day on Days 1 through 4 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks);
  2. 12 mcg/kg/day on Days 1, 8, and 15 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks)

ARM 2 is now closed. Patients experiencing clinical benefit (irSD, irPR, or irCR per irRC) after 4 cycles of treatment, may continue their denileukin diftitox treatment for up to 8 cycles.

Detailed Description:

This is a multicenter, open-label, dose/schedule and clinical efficacy study in patients with Stage IIIC and Stage IV melanoma.

Dose-Schedules: This is a schedule, dose, and pharmacodynamic study of Denileukin diftitox in in patients with Stage IIIC and Stage IV melanoma. Two arms of 40 patients each were originally planned (see below) for a total of 80 patients. Patients were randomly assigned to 1 of 2 arms: 1. 12 mcg/kg/day on Days 1 through 4 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks); 2. 12 mcg/kg/day on Days 1, 8, and 15 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks). Patients will be evaluated for (clinical response, safety and tolerability, and pharmacodynamic measures of ONTAK activity. An optional substudy will be conducted that will involve collection of serial tumor biopsies at study entry and Day 84 in order to assess tissue pharmacodynamic markers of ONTAK activity (Treg depletion in tumor, appearance of melanoma antigen-specific CD8+lymphocytes, and other markers of mucosal immunity and inflammatory response).

Following an amendment, patients will be enrolled in Arm 1 only (expanded to a total of 55 patients) and Arm 2 was closed. According to the original design, if two responses or less were observed among 22 patients on either arm, that arm would be discontinued.

Patients experiencing clinical benefit (immune-related stable disease [irSD], immune-related partial response [irPR], or immune-related complete response [irCR] per irRC) after 4 cycles of treatment, may continue their denileukin diftitox treatment for up to 8 cycles


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria Patients may be entered in the study only if they meet all of the following criteria.

  1. Male or female patients greater than or equal to18 years of age;
  2. Patients with histologically confirmed melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);
  3. Naive to prior systemic chemotherapy, targeted therapy (eg, BRAF), or immunotherapy (eg, interleukin-2 [IL-2] or interferon) for the treatment of melanoma, including any cytotoxic agents or IL-2 used for adjuvant therapy (adjuvant interferon is allowed). Prior granulocyte macrophage colony-stimulating factor (GM-CSF) is allowed;
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;
  5. Life expectancy greater than or equal to 3 months;
  6. At least 1 site of radiographically measurable disease by immune-related response criteria (irRC);
  7. Serum albumin greater than or equal to 3 g/dL;
  8. Adequate hematologic, renal, and liver function as defined by laboratory values performed within 21 days prior to initiation of dosing:

    • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L;
    • Platelet count greater than or equal to 100 x 10^9/L;
    • Hemoglobin greater than or equal to 9 g/dL;
    • Serum creatinine less than or equal 1.5 x upper limit of normal (ULN) or creatinine clearance greater than or equal to 50 mL/min;
    • Total serum bilirubin less than or equal to 1.5 x ULN;
    • Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT) less than or equal to 2.5 x ULN, and less than or equal to 5 x ULN if liver metastases are present.
  9. Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician;
  10. Pre-menopausal females and females less than 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of study drug. Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for greater than or equal to 1 year; Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.

Exclusion Criteria

Patients will not be entered in the study for any of the following:

  1. Known central nervous system (CNS) lesions, except for asymptomatic non-progressing, treated brain metastases.

    Treated brain metastases are defined as having no evidence of progression or hemorrhage for 2 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computerized tomography [CT]) during the Screening period (using the pretreatment brain image as Baseline). Treatment for brain metastases must have been completed at least 2 months prior to Day 1 of the first treatment cycle and may include whole brain radiotherapy, radiosurgery (Gamma Knife, LINAC, or equivalent), or a combination as deemed appropriate by the treating physician. Dexamethasone must be discontinued at least 4 weeks prior to Day 1. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 2 months prior to Day 1 will be excluded;

  2. Carcinomatous meningitis;
  3. Prior treatment with denileukin diftitox;
  4. Known hypersensitivity to denileukin diftitox or any of its components: diphtheria toxin, IL-2, or excipients;
  5. Prior surgery for melanoma less than 4 weeks before enrollment;
  6. Other malignancy within 3 years of randomization, with the exception of adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no subsequent evidence of recurrence and/or malignancies diagnosed at a stage where definitive therapy results in near certain cures. The Medical Monitor must be consulted in such cases;
  7. Currently receiving any other anticancer treatment for melanoma (including palliative radiotherapy);
  8. Received treatment in another clinical study within the 4 weeks prior to commencing study treatment or patients who have not recovered from side effects of an investigational drug to Common Terminology Criteria for Adverse Events (CTCAE) Grade less than or equal to 1, except for alopecia;
  9. Received radiotherapy for non-CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation-related toxicities to Grade less than or equal to 1, except for alopecia;
  10. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association [NYHA] Grade greater than 2 [see Appendix 5], unstable angina, or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
  11. Use of chronic systemic steroids (>5 days) within 2 weeks of Day 1 of the first treatment cycle (replacement therapy for adrenal insufficiency is allowed);
  12. Patients with an allograft requiring immunosuppression;
  13. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive;
  14. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures; Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01127451

United States, California
Encinitas, California, United States, 92008
Los Angeles, California, United States, 90025
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Maryland
Baltimore, Maryland, United States, 21237
United States, Michigan
Detroit, Michigan, United States, 48202
United States, Nebraska
Lincoln, Nebraska, United States, 68510
United States, Oregon
Portland, Oregon, United States, 97227
United States, Texas
Amarillo, Texas, United States, 79106
Sponsors and Collaborators
Eisai Inc.
PharmaBio Development Inc.
Study Director: Harish Dave, MD Quintiles, Inc.
  More Information

Responsible Party: Eisai Inc. Identifier: NCT01127451     History of Changes
Other Study ID Numbers: E7272-701
Study First Received: May 19, 2010
Last Updated: March 31, 2015

Keywords provided by Eisai Inc.:

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Denileukin diftitox
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs processed this record on May 25, 2017