E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and neck squamous cell carcinoma (HNSCC) |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent or secondary primary squamous cell carcinoma originating from the oral cavity, oro/hypo-pharynx or larynx |
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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 | 19.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and tolerability of nivolumab when administered concomitant with high dose (60 Gy) re-irradiation in patients with locally advanced recurrent or second primary HNSCC |
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E.2.2 | Secondary objectives of the trial |
To evaluate progression-free survival after 12 months. To evaluate objective response rate (ORR) and duration of response (DOR), by RECIST v1.1 as primary method and immune-related RECIST (irRECIST) as secondary method. To evaluate overall survival.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >18 years
• Recurrent or secondary primary squamous cell carcinoma originating from the oral cavity, oro/hypo-pharynx or larynx
• Prior radiotherapy (46-70Gy)
• Adequate newly obtained core or excisional biopsy of a recurrent tumor lesion
• Measurable disease
• Lesion available for biopsy during study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy > 12 months
• A minimum of 6 months since prior radiotherapy in the same area or minimum 4 weeks (28 days) since previous other cancer treatment
• Both HPV positive and HPV negative disease allowed
• Distant metastases allowed
• Adequate organ function based on clinical examination and lab values
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
• Women must not be breastfeeding
• WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half-lives. The terminal half-life of nivolumab is up to 25 days
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E.4 | Principal exclusion criteria |
• History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin, cervical cancer stage IB and stage I prostate cancer considered not necessary to treat
• Disease suitable for curative salvage surgery
• Treatment with any investigational medicinal product (IMP) that may interfere with the study treatment, within 4 weeks prior to first administration of study drug.
• Significant cardiac, pulmonary or other medical illness that would limit activity or survival
• Pregnancy or lactation.
• Known hypersensitivity to any of the components of the investigational product
• Patients who test positive for hepatitis B, C or HIV.
• Diagnosis of immunodeficiency or medical condition requiring systemic steroids or other forms of immunosuppressive therapy
• Autoimmune disease that has required systemic therapy within the past 2 years
• Any reason why, in the opinion of the investigator, the patient should not participate
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E.5 End points |
E.5.1 | Primary end point(s) |
1) To determine the safety and tolerability of nivolumab when administered concomitant with high dose (60 Gy) re-irradiation in patients with locally advanced recurrent or second primary HNSCC
2) To determine a safe dose of nivolumab when administered concomitant with high dose (60 Gy) re-irradiation in patients with locally advanced recurrent or second primary HNSCC
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time point for primary safety evaluation: 12 months |
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E.5.2 | Secondary end point(s) |
1) To evaluate progression-free survival after 12 months
2) To evaluate objective response rate (ORR) and duration of response (DOR), by RECIST v1.1 as primary method and immune-related RECIST (irRECIST) as secondary method
3) To evaluate overall survival
4) To investigate the immunological response, tumor evolution and dynamics in the tumor micrenvironment induced by the study therapy
5) To investigate biomarkers for development of clinical response, toxicity and immune response
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
To evaluate progression-free survival after 12 months |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | |
E.8.9.1 | In the Member State concerned days | |