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Trial record 1 of 1 for:    S1404
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High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02506153
First received: July 22, 2015
Last updated: March 22, 2017
Last verified: February 2017
  Purpose
This randomized phase III trial studies how well high-dose recombinant interferon alfa-2B or ipilimumab works compared with pembrolizumab in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Monoclonal antibodies, such as ipilimumab and pembrolizumab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether high-dose recombinant interferon alfa-2B or ipilimumab is more effective than pembrolizumab in treating patients with melanoma.

Condition Intervention Phase
Metastatic Non-Cutaneous Melanoma
Non-Cutaneous Melanoma
Recurrent Melanoma of the Skin
Recurrent Non-Cutaneous Melanoma
Stage III Mucosal Melanoma of the Head and Neck
Stage III Skin Melanoma
Stage IIIA Skin Melanoma
Stage IIIB Skin Melanoma
Stage IIIC Skin Melanoma
Stage IV Skin Melanoma
Stage IVA Mucosal Melanoma of the Head and Neck
Stage IVB Mucosal Melanoma of the Head and Neck
Stage IVC Mucosal Melanoma of the Head and Neck
Biological: Ipilimumab
Other: Laboratory Biomarker Analysis
Biological: Pembrolizumab
Other: Pharmacological Study
Other: Quality-of-Life Assessment
Biological: Recombinant Interferon Alfa-2b
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial Comparing Physician/Patient Choice of Either High Dose Interferon or Ipilimumab to MK-3475 (Pembrolizumab) in Patients With High Risk Resected Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • OS [ Time Frame: From date of randomization to date of death due to any cause, assessed up to 5 years ]
    Cox regression models will be used to estimate hazard ratios and calculate confidence intervals to compare treatment arms in the PD-L1 negative subgroup. In addition Cox regression models for OS will be used to estimate interaction terms between PD-L1 status and treatment arm. A restricted mean survival time analysis will be done as a supportive analysis.

  • PD-L1 status [ Time Frame: Baseline ]
    Cox regression models will be used to estimate hazard ratios and calculate confidence intervals to compare treatment arms in the PD-L1 negative subgroup. In addition Cox regression models for OS and RFS will be used to estimate interaction terms between PD-L1 status and treatment arm.

  • RFS [ Time Frame: From date of randomization to date of first documentation of progression or death due to any cause, assessed up to 5 years ]
    Cox regression models will be used to estimate hazard ratios and calculate confidence intervals to compare treatment arms in the PD-L1 negative subgroup. In addition Cox regression models for RFS will be used to estimate interaction terms between PD-L1 status and treatment arm. A restricted mean survival time analysis will be done as a supportive analysis.


Secondary Outcome Measures:
  • B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation status [ Time Frame: Baseline ]
    Pre-study BRAF mutation status on patients will be collected. BRAF mutation will be analyzed as a prognostic value as a covariate in Cox regression analyses and exponential-logistic cure regression models. In addition, BRAF mutation will be analyzed as a predictive factor by analyzing the interaction between mutation status and treatment in Cox regression models and in exponential-logistic cure regression model.

  • Change in quality of life [ Time Frame: Baseline to up to 5 years ]
    The EQ-5D-EL, FACT-BRM, FACIT-D, and Trial Outcome Index will be assessed at multiple time points. Longitudinal regression models (using mixed-effects models) will be used to evaluate changes over time.

  • Incidence of toxicity assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after the last study drug administration ]
    Toxicity rates will be estimated with a 95% confidence interval.

  • Long-term survival [ Time Frame: Up to 10 years ]
    Exponential-logistic cure regression models will be used to examine the association between known prognostic factors, including stage, and long-term survivor/cure status, and survival for patients who are not long-term survivors/cured.

  • Post-relapse therapy [ Time Frame: Up to 10 years ]
    Data on therapy after relapse will be collected for three years after relapse (or until 10 years after registration maximum). Therapies will be categorized into one of two categories: systemic or local. Specific therapies after relapse will be tabulated and summarized. Therapy after relapse will be analyzed as a time-dependent variable in Cox regression analyses for the endpoint of OS after relapse.


Estimated Enrollment: 1240
Study Start Date: October 2015
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (high-dose recombinant interferon alfa-2B, ipilimumab)

INDUCTION THERAPY: Patients receive high-dose recombinant interferon alfa-2B intravenously (IV) over 20 minutes on days 1-5. Treatment repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive high-dose recombinant interferon alfa-2B subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Biological: Recombinant Interferon Alfa-2b
Given IV and SC
Other Names:
  • Alfatronol
  • Glucoferon
  • Heberon Alfa
  • IFN alpha-2B
  • Interferon alfa 2b
  • INTERFERON ALFA-2B
  • Interferon Alpha-2b
  • Intron A
  • Sch 30500
  • Urifron
  • Viraferon
Experimental: Arm II (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475
Other: Pharmacological Study
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • STEP 1 REGISTRATION:
  • Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible
  • Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site; nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by hematoxylin and eosin (H & E) stained slides
  • Patients with multiple regional nodal basin involvement are eligible; gross or microscopic extracapsular nodal extension is permitted
  • Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present; patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and must have no evidence of disease at the primary site or must undergo re-resection of the primary site; a full lymphadenectomy meeting the criteria outlined is required for all node-positive patients including those with positive sentinel nodes; patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected; for all patients, all disease must have been resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma; patients must be registered within 98 days of the last surgery performed to render the patient free of disease; patients must be registered within 98 days of the last surgery performed to render the patient free of disease
  • Patients must have available and be willing to submit a minimum of five unstained slides from primary, lymph node, or metastatic site to determine PD-L1 expression; the tumor tissue must be adequate for PD-L1 testing (defined as >= 100 tumor cells as confirmed by the treating institution's local pathologist); this must be documented by having a pathologist sign the S1404 Local Pathology Review form prior to step 1 registration; the specimens may come from an archived block but must be submitted within 20 days from cutting the slides
  • Patients must be offered the opportunity to participate in specimen banking as outlined
  • Patients must be willing to have blood draws for PK/ADA analysis as outlined, should the patient be randomized to the MK-3475 arm
  • Patients may have received prior radiation therapy, including after the surgical resection; all adverse events associated with prior surgery and radiation therapy must have resolved to =< grade 1 prior to registration
  • Patients must not have received neoadjuvant treatment for their melanoma; patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, pegylated (PEG)-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
  • Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after step 2 registration
  • All patients must have disease-free status documented by a complete physical examination and imaging studies within 42 days prior to registration; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan that is of diagnostic quality (with or without brain) or a CT of the chest, abdomen and pelvis; for patients with melanoma arising from the head and neck, dedicated neck imaging (CT with IV contrast or PET-CT through the region) is required; if the patient has had unknown primary with disease in the axilla, neck imaging is required to assure region is clear of cancer; CT imaging should be done with intravenous contrast if there are no contraindications for it; any other clinically-indicated imaging studies if performed (e.g. bone scan) must show no evidence of disease
  • All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 90 days prior to registration; the brain CT or MRI should be performed with intravenous contrast (unless contraindicated)
  • Absolute neutrophil count (ANC) >= 1,500 microliter (mcL)
  • Platelets >= 100,000 mcL
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x IULN
  • Alkaline phosphatase =< 2 x IULN
  • Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min
  • Patients must have lactate dehydrogenase (LDH) performed within 42 days prior to registration
  • Patients must have Zubrod performance status =< 1
  • Patients must have a baseline electrocardiogram (ECG) performed within 42 days of registration that is normal or considered not clinically significant by the site investigator
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
  • Patients known to be human immunodeficiency virus (HIV) positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate cluster of differentiation 4 (CD4) counts (>= 350 mm^3), and serum HIV viral load of < 25,000 IU/ml; patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria
  • Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration
  • Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
  • Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing
  • Patients who are able to complete questionnaires in English must participate in the quality of life assessments; (those patients who cannot complete the quality of life questionnaires in English can be registered to S1404 without contributing to the quality of life studies)
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 2 REGISTRATION (RANDOMIZATION CRITERIA):
  • Patients must not be registered until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 working days of receiving the e-mail notification
  • Women of childbearing potential must plan to have a urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required
  • No tests or exams are required to be repeated for step 2 registration (randomization); however, patients who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration; for example, ANC is not required to be repeated between step 1 and step 2 registration, but the most recent ANC performed before step 2 registration is required to be >= 1,500 mcL
  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: NCT02506153

  Show 510 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kenneth Grossmann Southwest Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02506153     History of Changes
Other Study ID Numbers: NCI-2014-02676
NCI-2014-02676 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1404
S1404 ( Other Identifier: SWOG )
S1404 ( Other Identifier: CTEP )
U10CA180888 ( US NIH Grant/Contract Award Number )
Study First Received: July 22, 2015
Last Updated: March 22, 2017

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
Pembrolizumab
Interferons
Interferon-alpha
Antibodies, Monoclonal
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 23, 2017