Stage IIIC MelanomaPhase 2NCT01127451
Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma
A Phase 2 study testing Denileukin diftitox in people with Stage IIIC Melanoma and Stage IV Melanoma, run by Eisai Inc. at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIC Melanoma, Stage IV Melanoma
- What is being tested?
- Denileukin diftitox
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 10 sitesUnited States
- Study dates
- 22 Jun 2010to 7 Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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;
Show all 16Show fewer
- 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;
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Study site
Amarillo, Texas, 79106
Study site
Baltimore, Maryland, 21237
Study site
Chicago, Illinois, 60637
Study site
Detroit, Michigan, 48202
Study site
Encinitas, California, 92008
Study site
Lincoln, Nebraska, 68510
Study site
Los Angeles, California, 90025
Study site
Louisville, Kentucky, 40202
Study site
Portland, Oregon, 97227
Study site
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase II Open-Label, Multicenter Study of Denileukin Diftitox in Patients With Stage IIIC and Stage IV Melanoma
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.
Read the detailed description
This is a multicenter, open-label, dose/schedule and clinical efficacy study in participants with Stage IIIC and Stage IV melanoma.
Dose-Schedules: This is a schedule, dose, and pharmacodynamic study of Denileukin diftitox in participants with Stage IIIC and Stage IV melanoma. Two arms of 40 participants each were originally planned (see below) for a total of 80 participants. Participants 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). Participants 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, participants will be enrolled in Arm 1 only (expanded to a total of 55 participants) and Arm 2 was closed. According to the original design, if two responses or less were observed among 22 participants on either arm, that arm would be discontinued.
Participants 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.
- Conditions
- Stage IIIC Melanoma, Stage IV Melanoma
- Being tested
- Denileukin diftitox
- Keywords
- Neoplasms
- Medical subject headings
- Melanoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Denileukin diftitoxDrug
Denileukin diftitox intravenous infusion over 30-60 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Denileukin diftitox |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From the start of treatment up to 1 year 6 months
Secondary outcomes (7)
Progression Free Survival (PFS)
The PFS was defined as time from start of study treatment until immune-related progressive disease (irPD) or death. If the participant did not progress, the participant was censored at the date of last tumor assessment, known alive, or until starting a next line of therapy, whichever occurred first. PFS was assessed by irRC. irPD was defined as at least 25% increase in tumor burden relative to nadir (at any single time point) in 2 consecutive observations at least 4 weeks apart. The PFS was estimated using the Kaplan-Meier method. The median time (weeks) and the corresponding 90% confidence interval were estimated for each treatment group are reported.
Measured: 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
The PFS was defined as time from start of study treatment until irPD or death. If the participant did not progress, the participant was censored at the date of last tumor assessment, known alive, or until starting a next line of therapy, whichever occurred first. PFS was assessed by irRC. irPD was defined as at least 25% increase in tumor burden relative to nadir (at any single time point) in 2 consecutive observations at least 4 weeks apart. Percentage of participants with PFS at month 6 are reported and was estimated using the Kaplan-Meier method.
Measured: Month 6
Duration of Response
Duration of response was defined as the time from date of the first assessment demonstrating an irCR or irPR to date of the first assessment demonstrating progressive disease (PD), death, or withdrawal from study. In the absence of confirmation of death or PD, duration of response was censored at the last date of follow-up when the participant was known to be alive and have maintained a response. Duration of response was assessed by 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% or greater (confirmed in 2 observations at least 4 weeks apart). The duration of response was estimated using the Kaplan-Meier method.
Measured: 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)
The OS was defined as the time from the date of randomization until the date of death. OS was estimated by Kaplan-Meier method. The median time (weeks) and the corresponding 90% confidence interval were estimated for each treatment group were reported.
Measured: From the date of randomization until the date of death up to 1 year 6 months
Percentage of Participants With OS at 1 Year
The OS was defined as the time from the date of randomization until the date of death. OS at 1 year was estimated by Kaplan-Meier method. OS at 1 year was measured as the percentage of participants still alive at 1 year from the date of randomization.
Measured: From the date of randomization up to 1 year
Change From Baseline in CD4+CD127-/loCD25+CD152- Cells Expression Pattern at Weeks 12
Treg (regulatory T cells) from peripheral blood and tumor tissues were assessed for best immune-related response. Assessment of Treg cells was done by immunohistochemical (IHC) analysis. Change from baseline in CD4+CD127-/loCD25+CD152- (surface marker expressed in Treg cells) expression pattern, by treatment and immune-related response are reported.
Measured: Baseline, Week 12
Change From Baseline in CD4+CD127-/loCD25hiCD152- Cells Expression Pattern at Weeks 12
Treg (regulatory T cells) from peripheral blood and tumor tissues were assessed for best immune-related response. Assessment of Treg cells was done by IHC analysis. Change from baseline in CD4+CD127-/loCD25hiCD152- (surface marker expressed in Treg cells) expression pattern, by treatment and immune-related response are reported.
Measured: Baseline, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2010 (estimated)
- Study start22 Jun 2010
- Primary completion7 Apr 2015
- Study completion7 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IIIC MelanomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PharmaBio Development Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01127451
- Sponsor's protocol ID
- E7272-701
- Status last verified
- Mar 2022
- First submitted
- 19 May 2010
- Last updated
- 13 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label, Multicenter Study of Denileukin Diftitox in Patients With Stage IIIC and Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT01127451
- Acronym / sponsor ID
- E7272-701
- Conditions
- Stage IIIC Melanoma, Stage IV Melanoma
- Keywords
- Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- PharmaBio Development Inc.
- Study start
- 22 Jun 2010 (actual)
- Primary completion
- 7 Apr 2015 (actual)
- Study completion
- 7 Apr 2015 (actual)
- First posted
- 20 May 2010 (estimated)
- Results
- Posted 13 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, open-label, dose/schedule and clinical efficacy study in participants with Stage IIIC and Stage IV melanoma.
Dose-Schedules: This is a schedule, dose, and pharmacodynamic study of Denileukin diftitox in participants with Stage IIIC and Stage IV melanoma. Two arms of 40 participants each were originally planned (see below) for a total of 80 participants. Participants 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). Participants 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, participants will be enrolled in Arm 1 only (expanded to a total of 55 participants) and Arm 2 was closed. According to the original design, if two responses or less were observed among 22 participants on either arm, that arm would be discontinued.
Participants 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denileukin Diftitox on Days 1 to 4 | Experimental | Drug: Denileukin diftitoxParticipants 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). |
| Denileukin Diftitox on Days 1, 8, and 15 | Experimental | Drug: Denileukin diftitoxParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denileukin diftitoxDenileukin diftitox intravenous infusion over 30-60 minutes. | Drug | Denileukin Diftitox on Days 1 to 4, Denileukin Diftitox on Days 1, 8, and 15 |
Primary outcome
Percentage of Participants With Immune-related Overall Response Rate (irORR)
Time frame: From the start of treatment up to 1 year 6 months
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).
7 secondary outcomes
Progression Free Survival (PFS)
Time frame: 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
Time frame: Month 6
Duration of Response
Time frame: 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)
Time frame: From the date of randomization until the date of death up to 1 year 6 months
Percentage of Participants With OS at 1 Year
Time frame: From the date of randomization up to 1 year
Change From Baseline in CD4+CD127-/loCD25+CD152- Cells Expression Pattern at Weeks 12
Time frame: Baseline, Week 12
Change From Baseline in CD4+CD127-/loCD25hiCD152- Cells Expression Pattern at Weeks 12
Time frame: Baseline, Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Stage IIIC Melanoma
Active, not recruitingPhase 3
Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery
Melanoma of Unknown Primary, Recurrent Melanoma
Active, not recruitingPhase 2
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
Active, not recruitingPhase 1
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8
Active, not recruitingPhase 1
Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma
Metastatic Melanoma, Stage III Cutaneous Melanoma AJCC v7
RecruitingPhase 1
IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors
Advanced Endometrial Carcinoma, Advanced Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denileukin diftitox in people with Stage IIIC Melanoma and Stage IV Melanoma, run by Eisai Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Immune-related Overall Response Rate (irORR) (time frame: From the start of treatment up to 1 year 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2022.