Yervoy With Sylatron Unresectable Stage 3 or 4 Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to see how much of the drug Yervoy can be safely tolerated when it is given to people who are also receiving a drug called Sylatron. Investigators also wish to find out whether the addition of Yervoy increases the chance that Sylatron will cause a rise in the level of antibodies in the patient's blood that recognize their own tissues, known as autoimmune antibodies. Investigators also want to find out how likely it is that their tumor will shrink.

Official Title
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A Phase Ib Study of Yervoy With Sylatron for Patients With Unresectable Stages IIIB/C/IV Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Sylatron
* Drug: Yervoy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have cytologically or histologically-confirmed and unresectable melanoma, previously untreated systemically other than a BRAF inhibitor for metastatic disease, meeting one of the following American Joint Committee on Cancer (AJCC) staging criteria: AJCC Stage IV (Tany,Nany,M1); AJCC Stage IIIB/C patients with unresectable nodal/locoregional involvement; Patients with cutaneous, ocular or mucosal melanoma are eligible Must have adequate hepatic, renal and bone marrow function as defined by the following parameters obtained within 4 weeks prior to initiation of study treatment. Hematologic Criteria: white blood count (WBC) >/= 3.0 x 10^9/L, Platelet > 100 x 10^9/L, Hemoglobin >/= 9 g/dL or 5.6 mmol/L; Renal and Hepatic Functional Criteria: Serum creatinine < 2.0 mg/dL or < 140 μmol/L, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) < 2 times upper normal limit of laboratory normal (ULN) Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Must give informed consent according to institutional policy Must be willing to give written informed consent and must be able to adhere to dose and visit schedules Female patients of childbearing potential must be using a medically accepted method of birth control prior to Screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation). Females of childbearing potential should be counseled in the appropriate use of birth control while in this study. Females who are not currently sexually active must agree and consent to use one of the above-mentioned methods should they become sexually active while participating in the study. Female patients of childbearing potential must have a negative serum pregnancy test (beta-hCG) at Screening. Exclusion Criteria: Female patients who are pregnant, intend to become pregnant, or are nursing Previously treated with interferon alpha 2b, Sylatron or Yervoy therapy for melanoma Patients whose disease can be completely surgically resected Have not recovered from the effects of recent surgery Patients with a history of prior malignancy within the past 2 years other than surgically cured squamous or basal cell carcinoma of the skin, or cervical carcinoma in situ Have severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease Patients with thyroid dysfunction not responsive to therapy Patients who, in the opinion of the investigator, have uncontrolled diabetes mellitus Suffering from an active autoimmune disease except medically controlled hypothyroidism and vitiligo An active and/or uncontrolled infection, including active hepatitis Have a history of seropositivity for HIV Pre-existing psychiatric condition, including but not limited to: History of severe depression (including Hospitalization for depression, Electroconvulsive therapy for depression, Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions); Suicidal of homicidal ideation and/or suicidal or homicidal attempt; History of severe psychiatric disorders (e.g., psychosis, post-traumatic stress disorder or mania); Past history or current use of lithium and/or antipsychotic drugs A clinical diagnosis of substance abuse of the one or more of the following drugs, within the following timeframes, (not including time spent in detoxification, hospitalization or incarceration): Alcohol, intravenous drug use (IVDU), inhalational, psychotropics, narcotics, cocaine, prescription or over-the-counter drugs: within 1 year of the Screening visit; Receiving methadone, buprenorphine hydrochloride (HCL), and/or butorphanol tartrate within 1 year of Screening visit, unless participant has drug screen negative for other (non-narcotic) drugs documented in past year and repeated negative within 2 months of Screening visit; Multi-drug abuse (2 or more substances in 17a and 17b) within 3 years of Screening visit; If the patient's historic marijuana use is deemed excessive by the principal investigator (PI), or medically qualified individual or is interfering with the patient's life, then the patient is not eligible and should not be screened. If patient's marijuana use is not deemed excessive by PI and does not interfere with life, the patient must be instructed to discontinue any current use of recreational marijuana prior to entry into study. Patients with a medical condition requiring chronic systemic corticosteroids Known to be allergic to the drug substance or any of the excipients in the Sylatron or Yervoy formulation Patients who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study Have used any investigational drugs within 30 days of study entry Are participating in any other clinical treatment study

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yervoy with Sylatron<br>Participants are given Yervoy induction every 3 weeks for four doses, for 12 weeks, and all participants simultaneously receive Sylatron induction weekly, followed by Sylatron maintenance alone for up to 144 additional weeks (total 156 weeks = 3 years). | Drug: Sylatron<br>* Sylatron - Once per week for 12 weeks, given as an injection under the skin.<br>* Other names: PEG-Intron;Drug: Yervoy<br>* Yervoy - Once every 3 weeks for 12 weeks (4 times total), given over a 90-minute intravenous infusion (through the vein).<br>* Other names: Ipilimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Sylatron | MTD of peginterferon alfa-2b (Sylatron) combined with Ipilimumab (Yervoy). | Up to 48 Months | 
| Maximum Tolerated Dose (MTD) of Ipilimumab | MTD of Ipilimumab (Yervoy) combined with peginterferon alfa-2b (Sylatron). To assess the safety, toxicities and tolerability of a regimen of 3 μg/kg weekly Sylatron with concurrent induction Yervoy at 3 mg/kg, then if well tolerated, at 10 mg/kg every three weeks four times, in participants with unresectable stages IIIC/IV melanoma, and to define a well tolerated dose of Yervoy in that combination. | Up to 48 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response (OR) | Overall Response: Complete Response (CR) + Partial Response (PR) by immune-related response criteria (irRC). Immune Related CR (irCR): Complete disappearance of all lesions (whether measurable or not, and no new lesions, and confirmation by a repeat consecutive assessment no less than 4 weeks from date first documented. Immure Related PR (irPR): decrease in tumor burden >50% relative to baseline confirmed by repeat consecutive assessment at least 4 weeks later. | Up to 54 Months | 
| Progression Free Survival (PFS) | Immune Related Progressive Disease (irPD): increase in tumor burden >25% relative to nadir (minimum recorded tumor burden) confirmed by repeat consecutive assessment at least 4 weeks later. | Up to 54 Months | 
| Overall Survival (OS) | OS: The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. | Up to 54 Months | 
| Treatment Related Adverse Events (AEs) - Grade 3 to 5 | Percentage of participants with treatment related AEs, Grade 3 to 5. All adverse events, regardless of causality are also reported in the Serious Adverse Event/Other Adverse Event reporting area. | 4 Years, 1 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unresectable, stage 3, stage 4, autoimmune, antibodies