| Eligibility |
Inclusion Criteria:
1. Newly diagnosed, histologically proven squamous cell carcinoma of oropharynx T1 N1-N2
or T2-T3 N0 to N2 (AJCC 2018)
2. HPV positive status (positive staining for p16 in immunochemistry)
3. Presence of at least one measurable lesion according to RECIST v1.1 criteria (longest
diameter recorded =10 mm with CT scan)
4. No prior anticancer therapy for OSCC
5. Patient eligible for definitive radiochemotherapy
6. Age = 18 years
7. WHO performance status < 2 i.e. 0 or 1
8. Body weight >30kg
9. Life expectancy more than 3 months
10. Adequate Hematology laboratory data within 6 weeks prior to start of treatment:
Absolute neutrophils> 1.5 x 109/L, Platelets = 100 x 109/L, Hemoglobin = 9 g/dL
11. Adequate Biochemistry laboratory data within 6 weeks prior to start of treatment:
Total bilirubin = 1.5 x upper the normal limit, Transaminases = 2.5 xUNL, Alkalin
phosphatases = 5 x UNL, Creatinin clearance = 60 mL/min (Cockcroft), Glycemia = 1.5 x
UNL
12. Adequate Hemostasis laboratory data within 6 weeks prior to start of treatment: TP
within the normal range
13. Women should be post-menopaused or willing to accept the use an effective
contraceptive regimen during the treatment period and at least 3 months (durvalumab
arm) or 6 months (cisplatin arm) after the end of the study treatment. All
non-menopaused women should have a negative pregnancy test within 72 hours prior to
registration. Men should accept to use an effective contraception during treatment
period and at least 3 months (durvalumab arm) or 6 months (cisplatin arm) after the
end of the study treatment
14. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
15. Signed written informed consent
Exclusion Criteria:
1. T1 N0, T1-T3 N3, T4 N0-N3, p16 + OSCC
2. Previous treatment with another check-point inhibitor
3. Other histologies : UCNT, p16- SCCHN, sino-nasal tumors
4. Patient ineligible for Cisplatin according to the updated SmPC of the drug (including
patient with auditory deficiency, patient with neuropathy induced by previous
Cisplatin treatment or patient treated with prophylactic phenytoin)
5. Metastatic disease
6. Previous radiotherapy, except anterior strictly out of field radiotherapy, received
for treatment of another primary tumor considered in remission in the past 5 years
7. Participation in another therapeutic trial within the 30 days prior to entering this
study
8. Uncontrolled disease such as diabetes, hypertension, symptomatic congestive heart or
pulmonary failure, renal or hepatic chronic diseases... (non-exhaustive list)
9. Clinically significant cardiac disease or impaired cardiac function, such as:
- Congestive heart failure requiring treatment (New York Heart Association (NYHA)
Grade = 2), left ventricular ejection fraction (LVEF) < 50% as determined by
multi-gated acquisition (MUGA) scan or echocardiogram (ECHO), or uncontrolled
arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average
of 3 consecutive readings),
- History or current evidence of clinically significant cardiac arrhythmias, atrial
fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome,
high- Grade/complete AV-blockage
- Acute coronary syndromes (including myocardial infarction, unstable angina,
coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 3
months prior to screening
- QT interval adjusted according to Fredericia (QTcF) > 470 msec on screening ECG
10. Current or prior use of immunosuppressive medication within 28 days before the first
fraction of RT (exception: systemic corticosteroids at physiologic doses not exceeding
10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication
for hypersensitivity reactions (eg, CT scan premedication) - Topical, inhaled, nasal
and ophthalmic steroids are not prohibited)
11. Active suspected or prior documented autoimmune disease (including inflammatory bowel
disease, celiac disease, irritable bowel syndrome, Wegner's granulomatosis and
Hashimoto's thyroiditis, diverticulitis with the exception of diverticulosis, systemic
lupus erythematosus, Sarcoidosis syndrome). Note: participants with vitiligo or
alopecia, residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, patients with celiac disease controlled by diet alone, psoriasis not
requiring systemic treatment, or conditions not expected to recur in the absence of an
external trigger, are permitted to enroll
12. Known primary immunodeficiency or active HIV (positive HIV 1/2 antibodies)
13. Known active or chronic viral hepatitis or history of any type of hepatitis within the
last 6 months indicated by positive test for hepatitis B surface antigen (HBV sAG) or
hepatitis C virus ribonucleic acid (HCV antibody)
14. History of organ transplant requiring use of immunosuppressive medication
15. History of active tuberculosis (clinical evaluation that includes clinical history,
physical examination and radiographic findings, and TB testing in line with local
practice)
16. Current pneumonitis or interstitial lung disease
17. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, serious chronic gastrointestinal conditions associated with diarrhea, or
psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the ability of
the patient to give written informed consent
18. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease
19. History of severe allergic reactions to any unknown allergens or any components of the
study drug
20. History of leptomeningeal carcinomatosis
21. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician
22. Uncontrolled severe infectious disease, active hemorrhagic syndrome
23. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP
24. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
25. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
30 days after the last dose of IP
26. Vaccination for yellow fever
27. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after
the last dose of cisplatin
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