E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046885 |
E.1.2 | Term | Vaginal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061306 |
E.1.2 | Term | Nasopharyngeal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047777 |
E.1.2 | Term | Vulvar cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064025 |
E.1.2 | Term | Merkel cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study to investigate the safety and efficacy of using nivolumab, and nivolumab in combination with ipilimumab, to treat subjects who have virus-associated tumors. Certain viruses that infect human cells have been known to play a role in tumor formation and growth. This study will investigate the effects of the study drug nivolumab, and nivolumab in combination with ipilimumab, in human subjects who have the following types of tumors: Epstein Barr Virus (EBV) positive gastric cancer; EBV positive nasopharyngeal cancer (NPC); Human Papilloma Virus (HPV) positive cervical, vaginal, vulvar cancer; HPV positive squamous cell cancer of the head and neck (SCCHN); and Polyomavirus positive merkel cell cancer. |
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E.2.2 | Secondary objectives of the trial |
-To determine the percent change from baseline of immune cells and the percent change from baseline of select immune activation/inhibitory molecules of viral specific T cells in tumor specific subsets of nivolumab treated subjects.
-To evaluate the duration of response, progression-free survival and overall survival (monotherapy and combination therapy) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Blood Sample Amendment 01 dated 29-Apr-2015
The objective of this Amendment is to permit the collection and storage of blood Choice Placeholdersamples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA209358 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of virus-positive and virus-negative solid tumor samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
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E.3 | Principal inclusion criteria |
-Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types):
• Merkel Cell Carcinoma
• Gastric or Gastro-Esophageal junction carcinoma
• Nasopharyngeal Carcinoma
• Squamous cell carcinoma of the cervix, vagina, or vulva
• Squamous cell carcinoma of the Head and Neck
-Measurable disease by CT or MRI
-Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-Subject willing to comply to provide tumor tissue (archival or fresh biopsy specimen)
-Men and women of age 18 or older. |
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E.4 | Principal exclusion criteria |
-Active brain metastases or leptomeningeal metastases
-Subjects with active, known or suspected autoimmune disease
-Subjects with a condition requiring systemic treatment with either corticosteroids
-Subjects with hepatitis;Subjects with HIV
-Pregnant or breastfeeding women |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Safety: The proportion of subjects in the neoadjuvant cohort with surgery delayed > 4 weeks due to a drug-related AE.
-Efficacy: The investigator-assessed objective response rate (ORR) of nivolumab monotherapy and nivolumab plus ipilimumab combination therapy in subjects in the recurrent/metastatic cohorts. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Safety: Contingent on enrollment.
-Efficacy: ORR 6 months after the last patient receives their first dose |
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E.5.2 | Secondary end point(s) |
-To determine the percent change from baseline of immune cells and the percent change from baseline of select immune activation/inhibitory molecules of viral specific T cells in tumor specific subsets of nivolumab treated subjects.
-To evaluate the duration of response, progression-free survival, and overall survival in subjects treated with nivolumab monotherapy and subjects treated with nivolumab plus ipilimumab combination therapy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Contingent on enrollment. Rate of enrollment will determine timing for analyses. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments,Immunogenicity Assessments |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase I mainly safety/biomarker study (neoadjuvant cohort) |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Japan |
Korea, Republic of |
Netherlands |
Spain |
Taiwan |
Thailand |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end when survival follow-up has concluded. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 17 |