E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced resectable squamous cell carcinoma of the oral cavity |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071536 |
E.1.2 | Term | Head and neck cancer stage IV |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071537 |
E.1.2 | Term | Head and neck cancer stage III |
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071538 |
E.1.2 | Term | Head and neck cancer stage II |
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 evaluate the antitumor activity of pre-operative IPH2201 in patients with operable squamous cell carcinoma of the oral cavity |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of IPH2201, the pharmacokinetics, the immunogenicity and the pharmacodynamics including intra-tumoral biomarkers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria for inclusion into the study:
- Age ≥ 18 years
- Histologically confirmed HPV positive or negative, primary, previously untreated, resectable squamous cell carcinoma of the oral cavity considered clinically and radiologically as intermediate or high-risk, i.e. classified according to the AJCC classification as:
o Stage II with large (≥ 3 cm and ≤ 4cm) cT2cN0cM0 tumors or any cT2cN0cM0 tumor invading neighboring structures
o Stage III:
cT1cN1cM0
cT2cN1cM0
cT3cN0cM0 or cT3cN1cM0
o Stage IVa:
cT1cN2cM0
cT2cN2cM0
cT3cN2cM0
cT4acN0cM0 or cT4acN1cM0 or cT4acN2cM0
o Stage IV with a primary tumor (cT) of any stage and an adenopathy assessed as cN3 considered as resectable by the investigator surgeon and no clinically or radiologically detectable metastasis
- Good probability to achieve a R0 resection and to perform an adequate functional reconstruction
- Measurable lesion of the primary tumor and, if any, of lymph node metastasis
- ECOG 0-1
- Adequate bone marrow function
- Adequate liver function
- Adequate renal function
- Patients (male or female) who accept and are able to use recognized highly effective contraception methods throughout the study and up to 5 months after last dose of study drug
- Signed informed consent prior to any protocol-specific procédures
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E.4 | Principal exclusion criteria |
Patients will not be eligible for the study if they fulfil one or more of the following exclusion criteria:
- Squamous cell carcinoma of the oral cavity considered clinically and radiologically as stage I according to the AJCC classification
- Other ongoing malignancy including another location of squamous cell cancer outside the oral cavity
- History of previous malignancies corresponding to the following:
o any other head and neck cancer treated by radiotherapy;
o any other squamous cell carcinoma of the oral cavity;
o any other malignancy for which treatment has not allowed to achieve a complete remission, or for which complete remission was achieved less than 1 year before enrollment
o any other malignancy, even in complete remission, which treatment by chemo- and /or radiotherapy has been completed for less than one year
- Life expectancy <3 months
- Abnormal cardiac status
- Patients who are currently receiving medication with a known risk to prolong the QT interval or inducing Torsades de Pointes
- Current active or chronic infectious diseases, including positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen and/or negative anti-Hbs Antibody; active infection by mycobacterium tuberculosis; latent infection by mycobacterium tuberculosis with positive interferon gamma release assay irrespective of history of Bacillus Calmette Guérin (BCG) vaccination
- History of severe allergic, anaphylactic, or other hypersensitivity reaction to therapeutic antibodies, Chinese hamster ovary cell products or any of the constituents of IPH2201
- Administration of a live, attenuated vaccine, within 4 weeks prior to randomisation and for at least 5 half-lives after the last dose of study drug.
- Auto-immune disease, which currently or previously required systemic immunosuppressive or immunomodulatory therapy
- Serious concurrent uncontrolled medical disorder
- History of allogeneic stem cell or solid organ transplantation
- Intermittent or continuous renal replacement therapy
- Pregnant or lactating women
- Any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Any medical, psychological or other condition that restricts the reconnaissance or consent of the patient to voluntarily participate in this examination
- Persons who are housed in an institution due to governmental or judicial authorities
- Use of any investigational agent within 3 months prior to the first dosing
- Systemic treatment with corticosteroids or other immunosuppressive agents within 30 days prior to IPH2201 first administration |
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E.5 End points |
E.5.1 | Primary end point(s) |
Best objective response rate before surgery documented by imaging, and confirmed by independent radiologists, on the basis of RECIST 1.1 criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Pathologic complete response rate assessed in patients undergoing surgical removal of the tumor
- Separate assessment of the objective response rate, based on the RECIST criteria and documented by imaging in the primary tumor and in invaded lymph nodes, if any
- Progression-Free Survival (PFS) rate and Overall Survival (OS) rates
- Safety of IPH2201
- Documentation of the surgical delay due to adverse events.
- Assessment of the quality of life of the patients using the EORTC QLQ H&N35 questionnaire, at screening and end of treatment visits.
- Pharmacokinetic endpoints
- Pharmacodynamic endpoints
- Immunogenicity: occurrence of HAHA
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Tumor response assessments at weeks 4, 8, 20, 32, 44, 52
- PFS rate and OS rate 12 months after the first administration (then 2 additional years within the scope of a post study follow up)
- QoL: week 8
- Safety/PK/PD: each study visit |
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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 | 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) | 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 |
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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.8.3 |
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 | 12 |
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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End of Trial: Last Patient Last Visit |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |