Metastatic Melanoma
Conditions
Keywords
melanoma, metastatic, skin cancer, Stage IV, interleukin-2
Brief summary
Phase IV, open-label, randomized, two-arm, multi-center study in patients with metastatic melanoma who are treatment naïve or have previously received a single non-immunologic therapy. Treatment Arm 1: HD IL-2 first, then ipilimumab Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. Treatment Arm 2: Ipilimumab first then HD IL-2 Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2.
Detailed description
All patients will receive IL-2 at 600,000 international units per kilogram (kg) by intravenous bolus (IVB) every 8 hours for up to 14 planned doses with an additional cycle 14 days after the first. Ipilimumab 3mg/kg IV infusion Q3 weeks up to 4 doses4 doses A 3-6 week interval been the administration of the two drugs to allow for resolution of treatment-related toxicities. If corticosteroids were required during Ipilimumab administration, a 2-week period from discontinuation of steroid treatment to start of HD IL-2.
Interventions
DRUGHigh Dose Interleukin-2
DRUGIpilimumab
Sponsors
M.D. Anderson Cancer Center
Johns Hopkins University
Clinigen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
assess the sequenced use of HD IL2 and IPI in metastatic melanoma patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients 18 years or older * Confirmed and measurable metastatic melanoma with at least one measurable lesion for evaluation of response * Meets the requirements for HD IL-2 therapy per Institutional guidelines * Meets the requirements for ipilimumab therapy per Institutional guidelines * Treatment naïve or has received only one systemic therapy apart from adjuvant therapy. * At least 4 weeks since last adjuvant therapy or other cancer treatment * Willing and able to give informed consent and participate in study procedures as described in the 12PLK02 and 10PLK13 protocols. Patients consented for 12PLK02 will also be asked to participate in the 10PLK13 PROCLAIM registry study.
Exclusion criteria
* Patients with known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) or other infectious hepatitis * Pregnant, nursing or planning to become pregnant * Untreated brain metastases. (Brain metastases that have been treated, which no longer require corticosteroid therapy and are without progression by MRI at least 6 weeks after definitive therapy are acceptable.) * Received prior ipilimumab therapy (Prior Adjuvant Ipilimumab and Adjuvant Interferon are permitted with a minimum 4 week washout) * Received prior HD IL-2 therapy. * Received investigational drug within 30 days prior to study dosing. Patients may participate in non-interventional or observational clinical studies, including the 10PLK13 PROCLAIM registry study. * Concomitant disease or condition that would interfere with the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately | start of first treatment to date of death from any cause and patients alive at their last evaluation date were censored up to 1 year. | evaluable patients who received at least 50% of both research drugs and had their disease re-evaluated after baseline; defined in days for the start of the first treatment to death. percent of patients alive at 1 year; estimates were assessed using Kaplan-Meier method for the entire subject population for each treatment arm separately. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 5-11 weeks, 13-19 Weeks, 24-30 weeks and 1 year | duration of time (in Days) from start of the first treatment to the time of objective disease progression or death at one year. The immune-related response criteria (irRC) determined based on tumor burden calculated on the WHO method of multiplying the perpendicular dimensions of all lesions are summed to obtain the tumor burden. The total tumor burden + SPD (index lesions) + SPD (new measurable lesions) Based on CT scans and Physical exam at designated timepoints. CR- Disappearance of all known disease; PR\>/equal to decrease; SD Neither CR or PD; PD 25%increase; new lesion. |
Countries
United States
Participant flow
Recruitment details
Study initiation Sept 11, 2013 - Early Study Termination August 18, 2015 Planned accrual 50 pts/ arm.
Pre-assignment details
Patients will be randomized to receive both treatments in different sequence: Arm 1 IL-2 followed by Ipi; Arm 2 IPI followed by IL-2 Evaluable Patients will have received at least 50% of dose of both study drugs and completed assessment; Safety Population are all patients who received 1 dose of either study drug; Intent to treat
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm 1 IL-2 First Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab.
High Dose Interleukin-2
Ipilimumab | 13 |
| Treatment Arm 2 Ipi First Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2.
High Dose Interleukin-2
Ipilimumab | 16 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lack of Efficacy | 5 | 5 |
| Overall Study | non compliance, study closure | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Treatment Arm 2 Ipi First | Treatment Arm 1 IL-2 First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 26 Participants |
| Age, Continuous | 46 years | 49.5 years | 48 years |
| Region of Enrollment United States | 16 participants | 13 participants | 29 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 12 Participants | 8 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 2 / 16 |
| other Total, other adverse events | 9 / 13 | 10 / 16 |
| serious Total, serious adverse events | 9 / 13 | 10 / 16 |
Outcome results
Primary
Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately
evaluable patients who received at least 50% of both research drugs and had their disease re-evaluated after baseline; defined in days for the start of the first treatment to death. percent of patients alive at 1 year; estimates were assessed using Kaplan-Meier method for the entire subject population for each treatment arm separately.
Time frame: start of first treatment to date of death from any cause and patients alive at their last evaluation date were censored up to 1 year.
Population: patients who received at least 50% of both research drugs as planned-and had their disease re-evaluated after baseline; patients who exhibited PD or died before the end of one course of treatment were also considered evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1 | Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately | 73 percentage of participants |
| Treatment Arm 2 | Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately | 75 percentage of participants |
Comparison: OS rates of the Evaluable population in entire cohort was compared with the historical control rate of 46% (Hodi, et al NEJM 2010) using a one-sample binomial test due to early termination of enrollment without reaching target accrual; planned analysis to be the difference between treatment arms using log-rank test. One year OS along with 95% CI estimated for entire population and each treatment arm separately.p-value: 0.001Log Rank
Secondary
Progression-free Survival
duration of time (in Days) from start of the first treatment to the time of objective disease progression or death at one year. The immune-related response criteria (irRC) determined based on tumor burden calculated on the WHO method of multiplying the perpendicular dimensions of all lesions are summed to obtain the tumor burden. The total tumor burden + SPD (index lesions) + SPD (new measurable lesions) Based on CT scans and Physical exam at designated timepoints. CR- Disappearance of all known disease; PR\>/equal to decrease; SD Neither CR or PD; PD 25%increase; new lesion.
Time frame: 5-11 weeks, 13-19 Weeks, 24-30 weeks and 1 year
Population: Evaluable patients who received up to 50% of the planned cycles of therapy in both study drugs; comparison of the sequences of therapy between treatment arms
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm 1 | Progression-free Survival | 58 days |
| Treatment Arm 2 | Progression-free Survival | 80 days |