Clinical trial NCT02488759: An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors
Official title: Non-Comparative, Open-Label, Multiple Cohort, Phase 1/2 Study of Nivolumab Monotherapy and Nivolumab Combination Therapy in Subjects With Virus-Positive and Virus-Negative Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Various Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2015-07-02
Enrollment: 578
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study to investigate the safety and effectiveness of nivolumab, and nivolumab combination therapy, to treat patients who have virus-associated tumors. Certain viruses have been known to play a role in tumor formation and growth. This study will investigate the effects of the study drugs, in patients who have the following types of tumors:

* Anal canal cancer-No longer enrolling this tumor type
* Cervical cancer
* Epstein Barr Virus (EBV) positive gastric cancer-No longer enrolling this tumor type
* Merkel Cell Cancer
* Penile cancer-No longer enrolling this tumor type
* Vaginal and vulvar cancer-No longer enrolling this tumor type
* Nasopharyngeal Cancer - No longer enrolling this tumor type
* Head and Neck Cancer - No longer enrolling this tumor type


Eligibility criteria: Inclusion Criteria:

* Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types):

  1. Merkel Cell Carcinoma
  2. Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type)
  3. Nasopharyngeal Carcinoma
  4. Squamous cell carcinoma (SCC) of the cervix, vagina, or vulva
  5. Squamous cell carcinoma of the Head and Neck
  6. Squamous cell carcinoma of the anal canal and penis
  7. Recurrent/metastatic SCC of the cervix not amenable to curative treatment with surgery and/or radiation therapy who are unsuitable for platinum-based therapy may enroll in the cervical cancer Combination B expansion cohort
* Measurable disease by CT or MRI
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient willing to comply to provide tumor tissue (archival or fresh biopsy specimen)
* Men and women of age 18 or older

Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases
* Patients with active, known or suspected autoimmune disease
* Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
* Patients with hepatitis
* Patients with HIV
* Pregnant or breastfeeding women

Primary outcomes:
measure: Neoadjuvant: Number of Participants With Drug-Related Select Adverse Events (AEs)
timeFrame: From first dose to 30 days post last dose (Up to 2 months)
measure: Neoadjuvant: Number of Participants With Drug-Related Serious Adverse Events (SAEs)
timeFrame: From first dose to 30 days post last dose (Up to 2 months)
measure: Neoadjuvant: Rate of Surgery Delay
timeFrame: Day 29
measure: Metastatic: Investigator-Assessed Objective Response Rate (ORR)
timeFrame: From the date of first dose to the date of the initial objectively documented tumor progression or the date of the last tumor assessment prior to subsequent therapy (Up to 65 months)
Secondary outcomes:
measure: Metastatic: Investigator-Assessed Duration of Response (DoR)
timeFrame: From first confirmed response (complete response or partial response) to the date of the initial objectively documented tumor progression or death due to any cause, whichever occurs first (Up to 83 months)
measure: Metastatic: Overall Survival (OS)
timeFrame: From the first dosing date to the date of death (Up to 83 months)
measure: Metastatic: Investigator-Assessed Progression-Free Survival (PFS)
timeFrame: From the first dosing date to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 83 months)
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Local Institution - 0033
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0003
state: Georgia
city: Lutherville
country: United States
facility: Local Institution - 0023
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0002
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0019
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0020
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0035
state: Michigan
city: New York
country: United States
facility: Local Institution - 0036
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0022
state: North Carolina
city: Oklahoma City
country: United States
facility: Local Institution - 0005
state: Oklahoma
city: Portland
country: United States
facility: Local Institution - 0004
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution - 0029
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Local Institution - 0001
state: South Dakota
city: Seattle
country: United States
facility: Local Institution - 0021
state: Washington
city: Brussels
country: Belgium
facility: Local Institution - 0012
city: Brussels
country: Belgium
facility: Local Institution - 0014
city: Bruxelles
country: Belgium
facility: Local Institution - 0013
city: Marseille Cedex 9
country: France
facility: Local Institution - 0031
city: Paris
country: France
facility: Local Institution - 0038
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0032
city: Vlllejuif
country: France
facility: Local Institution - 0030
city: Essen
country: Germany
facility: Local Institution - 0027
city: Heilbronn
country: Germany
facility: Local Institution - 0028
city: Kashiwa-shi
country: Japan
facility: Local Institution - 0039
state: Chiba
city: Chuo-ku
country: Japan
facility: Local Institution - 0040
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0041
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0024
city: Mexico City
country: Mexico
facility: Local Institution - 0056
state: Distrito Federal
city: Oaxaca de Juarez
country: Mexico
facility: Local Institution
state: Oaxaca
city: Merida
country: Mexico
facility: Local Institution - 0046
state: Yucatan
city: Amsterdam
country: Netherlands
facility: Local Institution - 0011
city: Utrecht
country: Netherlands
facility: Local Institution - 0034
city: Barcelona
country: Spain
facility: Local Institution - 0018
city: Madrid
country: Spain
facility: Local Institution - 0017
city: Navarra
country: Spain
facility: Local Institution - 0016
city: Tainan
country: Taiwan
facility: Local Institution - 0037
city: Taipei
country: Taiwan
facility: Local Institution - 0026
city: Glasgow
country: United Kingdom
facility: Local Institution - 0006
state: Lanarkshire
city: Birmingham
country: United Kingdom
facility: Local Institution - 0010
state: West Midlands
city: London
country: United Kingdom
facility: Local Institution - 0008
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Ferris RL, Spanos WC, Leidner R, Goncalves A, Martens UM, Kyi C, Sharfman W, Chung CH, Devriese LA, Gauthier H, Chiosea SI, Vujanovic L, Taube JM, Stein JE, Li J, Li B, Chen T, Barrows A, Topalian SL. Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial. J Immunother Cancer. 2021 Jun;9(6):e002568. doi: 10.1136/jitc-2021-002568.
citation: Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbe C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial. J Clin Oncol. 2020 Aug 1;38(22):2476-2487. doi: 10.1200/JCO.20.00201. Epub 2020 Apr 23.
citation: Naumann RW, Hollebecque A, Meyer T, Devlin MJ, Oaknin A, Kerger J, Lopez-Picazo JM, Machiels JP, Delord JP, Evans TRJ, Boni V, Calvo E, Topalian SL, Chen T, Soumaoro I, Li B, Gu J, Zwirtes R, Moore KN. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. J Clin Oncol. 2019 Nov 1;37(31):2825-2834. doi: 10.1200/JCO.19.00739. Epub 2019 Sep 5.
citation: Appelbaum J, Wells D, Hiatt JB, Steinbach G, Stewart FM, Thomas H, Nghiem P, Kapur RP, Thompson JA, Bhatia S. Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report. J Immunother Cancer. 2018 Aug 31;6(1):82. doi: 10.1186/s40425-018-0396-9.