Yervoy With Sylatron Unresectable Stage 3 or 4 Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01496807
First received: December 19, 2011
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Sylatron
Drug: Yervoy
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Study of Yervoy With Sylatron for Patients With Unresectable Stages IIIB/C/IV Melanoma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 48 Months ] [ Designated as safety issue: Yes ]
    To assess the safety, toxicities and tolerability of a regimen of 3 mcg/kg weekly Sylatron with concurrent induction Yervoy at 3, 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, if any.


Secondary Outcome Measures:
  • Rate of Induction of Autoimmune Antibodies [ Time Frame: 48 Months ] [ Designated as safety issue: No ]

    This study is not designed to statistically test the efficacy of treatment, and no inferential analyses will be performed.

    Autoimmune antibody parameters will be listed and summarized using means, standard deviations, and percentage coefficients of variation. Investigators wish to look for evidence of serologic and clinical autoimmunity.


  • Number of Participants With Overall Response (OR) [ Time Frame: 48 Months ] [ Designated as safety issue: No ]
    Overall response by both immune-related response criteria (irRC) and Modified World Health Organization (mWHO) will also be assessed as a secondary endpoint.


Estimated Enrollment: 36
Study Start Date: March 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Yervoy with Sylatron
Participants are randomized to Yervoy induction at 3 mg/kg every 3 weeks for four doses for 12 weeks, and all patients simultaneously receive Sylatron induction at 3 μg/kg/week) for 8 weeks, followed by Sylatron. Participants will receive Yervoy induction therapy for 12 weeks and Sylatron therapy for up to 156 weeks, or until disease progression, unacceptable toxicity or patient decision to discontinue.
Drug: Sylatron
Sylatron - Once per week for 12 weeks (while receiving Yervoy), given as an injection under the skin. Both groups will receive the SAME dose of Sylatron.
Other Name: PEG-Intron
Drug: Yervoy

Yervoy - Once every 3 weeks for 12 weeks (4 times total), given over a 90-minute intravenous infusion (through the vein). The 2 groups will receive DIFFERENT doses of Yervoy as outlined below.

Group 1: Yervoy, 3 milligrams (mg) per kilogram (kg) of body weight, every 3 weeks for 12 weeks (4 times).

Group 2: Yervoy, 10 milligrams (mg) per kilogram (kg) of body weight, every 3 weeks for 12 weeks (4 times).

Other Name: Ipilimumab
Active Comparator: Group 2: Yervoy with Sylatron
Participants are randomized to Yervoy induction at 10 mg/kg every 3 weeks for four doses for 12 weeks, and all patients simultaneously receive Sylatron induction at 3 μg/kg/week) for 8 weeks, followed by Sylatron. Participants will receive Yervoy induction therapy for 12 weeks and Sylatron therapy for up to 156 weeks, or until disease progression, unacceptable toxicity or patient decision to discontinue.
Drug: Sylatron
Sylatron - Once per week for 12 weeks (while receiving Yervoy), given as an injection under the skin. Both groups will receive the SAME dose of Sylatron.
Other Name: PEG-Intron
Drug: Yervoy

Yervoy - Once every 3 weeks for 12 weeks (4 times total), given over a 90-minute intravenous infusion (through the vein). The 2 groups will receive DIFFERENT doses of Yervoy as outlined below.

Group 1: Yervoy, 3 milligrams (mg) per kilogram (kg) of body weight, every 3 weeks for 12 weeks (4 times).

Group 2: Yervoy, 10 milligrams (mg) per kilogram (kg) of body weight, every 3 weeks for 12 weeks (4 times).

Other Name: Ipilimumab

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (eg, 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, ie. 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 (eg, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496807

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Jeffrey Weber, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01496807     History of Changes
Other Study ID Numbers: MCC-16755
Study First Received: December 19, 2011
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
unresectable
stage 3
stage 4
autoimmune
antibodies

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014