Yervoy With Sylatron Unresectable Stage 3 or 4 Melanoma

NCT01496807 | Completed Phase 1 Results DMC

• 1 other identifier: MCC-16755
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

unresectable; stage 3; stage 4; autoimmune; antibodies

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Number of Participants With Overall Response (OR)

  Up to 54 Months

• Progression Free Survival (PFS)

  Up to 54 Months

• Overall Survival (OS)

  Up to 54 Months

• Treatment Related Adverse Events (AEs) - Grade 3 to 5

  4 Years, 1 Month

Other Outcomes (1)

• Count of Participants Developing Positive Autoantibody Screen

  Up to 54 Months

Study Arms (1)

Yervoy with Sylatron

EXPERIMENTAL

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; Drug: Yervoy

Interventions

Sylatron DRUG

Sylatron - Once per week for 12 weeks, given as an injection under the skin.

Also known as: PEG-Intron

Yervoy with Sylatron

Yervoy DRUG

Yervoy - Once every 3 weeks for 12 weeks (4 times total), given over a 90-minute intravenous infusion (through the vein).

Also known as: Ipilimumab

Yervoy with Sylatron

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Brohl AS, Khushalani NI, Eroglu Z, Markowitz J, Thapa R, Chen YA, Kudchadkar R, Weber JS. A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma. J Immunother Cancer. 2016 Dec 20;4:85. doi: 10.1186/s40425-016-0194-1. eCollection 2016.

  PMID: 28031816 DERIVED

Related Links

• A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma

MeSH Terms

Conditions

Melanoma

Interventions

peginterferon alfa-2b; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Andrew Brohl
• Organization: H. Lee Moffitt Cancer Center and Research Institute

andrew.brohl@moffitt.org

813-745-3242

Study Officials

• Andrew Brohl, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2011
• First Posted: December 21, 2011
• Study Start: February 17, 2012
• Primary Completion: March 16, 2016
• Study Completion: August 29, 2016
• Last Updated: April 28, 2017
• Results First Posted: April 28, 2017

Record last verified: 2017-01

Locations

US (1)