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

NCT01127451 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E7272-701
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to determine whether participants with Stage IIIC and Stage IV Melanoma experience benefit when treated with Denileukin diftitox in two different dosing schedules.

Conditions

Stage IIIC Melanoma; Stage IV Melanoma

Keywords

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Immune-related Overall Response Rate (irORR)

  irORR was defined as the percentage of participants with best confirmed response (immune-related complete response \[irCR\] or immune-related partial response \[irPR\]). irORR was assessed by immune-related response criteria (irRC). Per irRC criteria, irCR was defined as complete disappearance of all tumor lesions, whether measurable or not, and no new lesions. irPR was defined as decrease in tumor burden by 50 percent (%) or greater (confirmed in 2 observations at least 4 weeks apart).

  From the start of treatment up to 1 year 6 months

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From the start of treatment to the date of first documentation of irPD, or date of death, whichever occurred first up to 1 year 6 months

• Percentage of Participants With PFS at Month 6

  Month 6

• Duration of Response

  From date of the first demonstration of irCR or irPR until the date of first demonstration of PD, date of death, or withdrawal from study up to 1 year 6 months

• Overall Survival (OS)

  From the date of randomization until the date of death up to 1 year 6 months

• Percentage of Participants With OS at 1 Year

  From the date of randomization up to 1 year

Study Arms (2)

Denileukin Diftitox on Days 1 to 4

EXPERIMENTAL

Participants received Denileukin Diftitox 12 mcg/kg/day (microgram per kilogram) on Days 1 through 4 of each 21-day treatment cycle, for a total of 4 cycles (12 weeks).

Drug: Denileukin diftitox

Denileukin Diftitox on Days 1, 8, and 15

EXPERIMENTAL

Participants received Denileukin Diftitox 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 was closed. Participants 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.

Drug: Denileukin diftitox

Interventions

Denileukin diftitox DRUG

Denileukin diftitox intravenous infusion over 30-60 minutes.

Denileukin Diftitox on Days 1 to 4; Denileukin Diftitox on Days 1, 8, and 15

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants greater than or equal to18 years of age;
• Participants with histologically confirmed melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);
• 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;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;
• Life expectancy greater than or equal to 3 months;
• At least 1 site of radiographically measurable disease by immune-related response criteria (irRC);
• Serum albumin greater than or equal to 3 g/dL;
• 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.
• 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;

You may not qualify if:

• Participants will not be entered in the study for any of the following:
• 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. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 2 months prior to Day 1 will be excluded;
• Carcinomatous meningitis;
• Prior treatment with denileukin diftitox;
• Known hypersensitivity to denileukin diftitox or any of its components: diphtheria toxin, IL-2, or excipients;
• Prior surgery for melanoma less than 4 weeks before enrollment;
• 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;
• Currently receiving any other anticancer treatment for melanoma (including palliative radiotherapy);
• Received treatment in another clinical study within the 4 weeks prior to commencing study treatment or participants 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;
• 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;
• 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);
• 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);
• Participants with an allograft requiring immunosuppression;
• Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive;

Sponsors & Collaborators

• Eisai Inc.: lead
• PharmaBio Development Inc.: collaborator

Study Sites (10)

Unknown Facility

Encinitas, California, 92008, United States

Location

Unknown Facility

Los Angeles, California, 90025, United States

Location

Unknown Facility

Washington D.C., District of Columbia, 20010, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Louisville, Kentucky, 40202, United States

Location

Unknown Facility

Baltimore, Maryland, 21237, United States

Location

Unknown Facility

Detroit, Michigan, 48202, United States

Location

Unknown Facility

Lincoln, Nebraska, 68510, United States

Location

Unknown Facility

Portland, Oregon, 97227, United States

Location

Unknown Facility

Amarillo, Texas, 79106, United States

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

denileukin diftitox

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 20, 2010
• Study Start: June 22, 2010
• Primary Completion: April 7, 2015
• Study Completion: April 7, 2015
• Last Updated: April 13, 2022
• Results First Posted: April 13, 2022

Record last verified: 2022-03

Locations

US (10)