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Trial record 1 of 1 for:    EA6141
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Nivolumab and Ipilimumab With or Without Sargramostim in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

This study has suspended participant recruitment.
(Scheduled Interim Monitoring)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02339571
First Posted: January 15, 2015
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This randomized phase II/III trial studies the side effects and best dose of nivolumab and ipilimumab when given together with or without sargramostim and to see how well they work in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab and nivolumab, may kill tumor cells by blocking blood flow to the tumor, by stimulating white blood cells to kill the tumor cells, or by attacking specific tumor cells and stop them from growing or kill them. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Condition Intervention Phase
Recurrent Melanoma of the Skin Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Questionnaire Administration Biological: Sargramostim Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II/III Study of Nivolumab Plus Ipilimumab Plus Sargramostim Versus Nivolumab Plus Ipilimumab in Patients With Unresectable Stage III or Stage IV Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Time Frame: Time from randomization to death from any cause, assessed up to 5 years ]
    Overall survival between the two arms will be compared using the stratified log-rank test. One-sided type I error rate of 0.2 will be used. Kaplan-Meier plot will be generated and two-sided p-values will be reported. This analysis will be summarized using the forest plots with hazard ratios and 95% confidence intervals. Cox multivariate models will be developed for overall survival.


Secondary Outcome Measures:
  • Clinical response, assessed using the utility of Immune related response criteria [ Time Frame: Up to 5 years ]
    Standard response criteria (based on the Response Evaluation Criteria in Solid Tumors) will be applied to assess clinical response. The Immune related response criteria and the Response Evaluation Criteria in Solid Tumors-based clinical response data will be compared between the two treatment arms, using the Fisher's exact test. Two-sided p-values will be reported. Furthermore Immune related response criteria data will be associated with the Response Evaluation Criteria in Solid Tumors-based clinical response. The Kappa statistics which measures the degree of agreement between the Response Eva

  • Immune response, assessed using the utility of Immune related response criteria [ Time Frame: Up to 5 years ]
    The Immune related response criteria and the Response Evaluation Criteria in Solid Tumors-based clinical response data will be compared between the two treatment arms, using the Fisher's exact test. Two-sided p-values will be reported. Furthermore Immune related response criteria data will be associated with the Response Evaluation Criteria in Solid Tumors-based clinical response. The Kappa statistics which measures the degree of agreement between the Response Evaluation Criteria in Solid Tumors-based response and Immune related response criteria will be estimated. McNemar's test will be use

  • Incidence of toxicities, defined using the Common Terminology Criteria for Adverse Events version 4.0 criteria [ Time Frame: Up to 90 days after the last study drug administration ]
    Individual toxicity type adverse event and categorized adverse event data (by autoimmune disorders, endocrine, gastrointestinal, liver, nervous system, pancreas, psychiatric disorders, skin, thromboembolic disorders) will be summarized by grade and treatment arm. The percentages of patients experiencing the worst degree toxicities (highest grade event per adverse event type per patient) will be evaluated and the distribution of the worst degree toxicities will be compared among the treatment arms. The proportion of patients with worst degree toxicities with 3 or higher will be summarized and c

  • Progression free survival, evaluated based on international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) [ Time Frame: Time from randomization to disease progression or death (whichever occurs first), assessed up to 5 years ]
    This analysis will be summarized using the forest plots with hazard ratios and 95% confidence intervals. Cox multivariate models will be developed for progression free survival.


Estimated Enrollment: 400
Actual Study Start Date: September 10, 2015
Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (nivolumab, ipilimumab, sargramostim)

INDUCTION THERAPY: Patients receive nivolumab IV over 60 minutes on day 1, ipilimumab IV over 90 minutes on day 1, and sargramostim SC on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive nivolumab and sargramostim as in Induction therapy. Patients with PR, SC, or CR at 24 weeks may continue maintenance therapy for up to 2 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
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Other: Questionnaire Administration
Ancillary studies
Biological: Sargramostim
Given SC
Other Names:
  • 23-L-Leucinecolony-Stimulating Factor 2
  • DRG-0012
  • Leukine
  • Prokine
  • rhu GM-CFS
  • Sagramostim
  • Sargramostatin
Experimental: Arm II (nivolumab, ipilimumab)

INDUCTION THERAPY: Patients receive nivolumab and ipilimumab as in Arm I. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive nivolumab as in Induction therapy. Patients with PR, SD, or CR at 24 weeks may continue maintenance therapy for up to 2 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
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Other: Questionnaire Administration
Ancillary studies

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
  • Patients must have known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status of tumor; wild-type (WT) or mutated, prior to randomization
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for at least one week prior to the start of the research study, and continuing for 5 months for women of childbearing potential and 7 months for sexually active males after the last dose of the study drugs
  • Patients must have unresectable stage III or stage IV melanoma; patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive
  • Patients must have measurable disease per RECIST 1.1 criteria; all sites of disease must be evaluated within 4 weeks prior to randomization
  • Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, BRAF, or mitogen-activated protein kinase [MEK] agents); patients may have had prior anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment; patients may not have had any prior programmed cell death (PD)-1/PD-ligand (PD-L)1 agent in the adjuvant setting
  • Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the metastatic setting
  • Patients must have discontinued chemotherapy, immunotherapy or other investigational agents used in the adjuvant setting >= 4 weeks prior to randomization and recovered from adverse events due to those agents; mitomycin and nitrosoureas must have been discontinued at least 6 weeks prior to entering the study; patients must have discontinued radiation therapy >= 2 weeks prior to entering the study and recovered from any adverse events associated with treatment; prior surgery must be >= 4 weeks from randomization and patients must be fully recovered from post-surgical complications
  • Patients must not receive any other investigational agents while on study or within four weeks prior to randomization
  • Patients are excluded for receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to four weeks (28 days) prior to or after any dose of ipilimumab; NOTE: Patients are permitted to receive the seasonal influenza vaccine; if seasonal influenza vaccine is considered, killed vaccines should be recommended
  • Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least 4 weeks following treatment and within 4 weeks prior to randomization are eligible; patients must not have taken any steroids =< 14 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
  • Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for > 3 years prior to the time of randomization
  • White blood count >= 3,000/uL
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40 ml/min
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN for patients with documented liver metastases)
  • Alkaline phosphatase =< 2 x ULN (=< 5 x ULN for patients with known liver involvement and =< 7 x ULN for patients with known bone involvement)
  • Total bilirubin =< 1.5 x ULN except subjects with normal direct bilirubin or those with known Gilbert's syndrome
  • Serum lactate dehydrogenase (LDH) =< 10 X ULN
  • Patients must not have any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), including but not limited to, ongoing or active infection requiring parenteral antibiotics on day 1, history of bleeding diathesis or need for concurrent anticoagulation (international normalized ratio [INR] =< 1.5 and partial thromboplastin time [PTT] within 1.1 x ULN), or psychiatric illness/social situations that would limit compliance with study requirements, interfere with subject's safety, or obtaining informed consent
  • Patients with human immunodeficiency virus (HIV) infection are ineligible
  • Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are not eligible; patients with cleared HBV and HCV (0 viral load) infection will be allowed
  • Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
  • Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); other CNS autoimmune disease (e.g., multiple sclerosis)
  • Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
  • Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed)
  • Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of the study drugs hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients must not have an active infection requiring current treatment with parenteral antibiotics
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339571


  Show 437 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Frank Hodi ECOG-ACRIN Cancer Research Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02339571     History of Changes
Other Study ID Numbers: NCI-2014-02674
NCI-2014-02674 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA6141
EA6141 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA6141 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Submitted: January 12, 2015
First Posted: January 15, 2015
Last Update Posted: November 21, 2017
Last Verified: November 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
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs