Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma

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.
 
ClinicalTrials.gov Identifier: NCT02723006
Recruitment Status : Terminated (Business decision: Protocol efficacy futility met)
First Posted : March 30, 2016
Results First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to determine the initial safety profile and initial antitumor activity of the combination treatments (immune checkpoint inhibitors [nivolumab, ipilimumab] with investigational drugs [TAK-580, TAK-202 (plozalizumab), vedolizumab]) in the 3 arms when administered to participants with advanced melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Drug: TAK-580 Drug: TAK-202 Drug: vedolizumab Drug: nivolumab Drug: ipilimumab Phase 1

Detailed Description:

The drugs being tested in this study are called TAK-580, TAK-202 (plozalizumab), and vedolizumab. These investigational drugs were given along with standard of care checkpoint inhibitors ([nivolumab in Arms 1 and 2] or nivolumab + ipilimumab in Arm 3). This study looked at the safety profile of the combination treatments in each arm when administered to participants with metastatic melanoma.

The study planned to enroll approximately 156 participants. Participants were assigned to one of the 3 treatment groups:

  • TAK-580 + nivolumab
  • TAK-202 (plozalizumab) + nivolumab
  • vedolizumab + nivolumab + ipilimumab

This study consists of 3 parts. A dose-escalation safety lead-in phase, confirmatory safety phase and a cohort expansion phase. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 50 weeks. Participants may make multiple visits to the clinic and 30, 60, and 90 days after last dose of study drug for follow-up assessments.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma
Actual Study Start Date : June 22, 2016
Actual Primary Completion Date : May 11, 2018
Actual Study Completion Date : May 11, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: TAK-580 + nivolumab
TAK-580 orally, once weekly along with nivolumab, intravenous, every 2 weeks.
Drug: TAK-580
TAK-580 tablets
Other Name: MLN2480

Drug: nivolumab
nivolumab infusion
Other Name: Opdivo

Experimental: TAK-202 (plozalizumab) + nivolumab
TAK-202 (plozalizumab) 2 milligram (mg), intravenous, once in Week 1, 3, 5, 9, and every 4 weeks thereafter with nivolumab infusion, intravenous, every 2 weeks.
Drug: TAK-202
TAK-202 infusion
Other Names:
  • MLN1202
  • plozalizumab

Drug: nivolumab
nivolumab infusion
Other Name: Opdivo

Experimental: vedolizumab + nivolumab + ipilimumab
Vedolizumab intravenous, once in Week 1, 3, 5, and 13 along with nivolumab infusion, intravenous, once in Week 1, 4, 7, 10, and 13 and every 2 weeks thereafter, along with ipilimumab intravenous, once in Week 1, 4, 7, and 10.
Drug: vedolizumab
vedolizumab infusion
Other Name: Entyvio

Drug: nivolumab
nivolumab infusion
Other Name: Opdivo

Drug: ipilimumab
ipilimumab infusion
Other Name: Yervoy




Primary Outcome Measures :
  1. Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase [ Time Frame: TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7 ]
    DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase [ Time Frame: Baseline up to Week 50 ]
    ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.

  2. Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50) ]
    DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

  3. Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50) ]
    PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions.

  4. Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From first dose of study drug until date of death from any cause (up to Week 50) ]
    OS was the time from date of first dose of study drug until date of death from any cause.

  5. Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50) ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is a male or female participant of 18 years or older.
  2. Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system.
  3. Has an eastern cooperative oncology group (ECOG) performance status of 0-1.
  4. Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters.
  5. For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies.
  6. Additional Inclusion Requirements for TAK-580 + nivolumab

    a) BRAF V600 mutation-positive or NRAS mutation-positive disease previously untreated with RAF, MEK, or other inhibitors of the mitogen-activated protein kinase (MAPK) pathway. Participants who have progressed on these agents can still be enrolled in TAK-202 (plozalizumab) + nivolumab or vedolizumab + nivolumab + ipilimumab.

  7. Additional Inclusion Requirements for expansion cohorts only a) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1) and at least 1 nonsignificant risk, non-target lesion accessible for biopsy per the guidelines above (for TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only).

Exclusion Criteria:

  1. Has active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (greater than [>] 10 milligram per day [mg/day] prednisone equivalents) for at least 2 weeks prior to study drug administration.
  2. Completed a prior therapy less than (<) 2 weeks prior to first dose and for whom adverse events (AEs) related to prior therapy had not returned to baseline or improved to Grade 1.
  3. Has active, known or suspected autoimmune disease.
  4. Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
  5. Has a history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis (including pneumonitis), interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  6. Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C.
  7. Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580)

    1. Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.
    2. Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.
    3. Left ventricular ejection fraction (LVEF) <50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.
    4. Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580.
  8. Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab)

    1. Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.
    2. Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease.
    3. Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine.

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): NCT02723006


Locations
Layout table for location information
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States
United States, California
University of California Los Angeles - Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
University of California San Francisco Medical Center
San Francisco, California, United States
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
United States, Minnesota
Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States
United States, New York
New York University Langone Medical Center
New York, New York, United States
United States, Pennsylvania
Saint Luke's Cancer Center - Bethlehem
Easton, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States
United States, Virginia
Inova Fairfax Hospital
Fairfax, Virginia, United States
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Layout table for additonal information
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02723006    
Other Study ID Numbers: C28003
U1111-1177-4142 ( Other Identifier: WHO )
2015-005554-35 ( EudraCT Number )
First Posted: March 30, 2016    Key Record Dates
Results First Posted: April 1, 2021
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nivolumab
Ipilimumab
Vedolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Gastrointestinal Agents