Cisplatin or ImmunoTHerapy in Association With Definitive Radiotherapy in HPV-related oropharyngEal Squamous Cell Carcinoma: a Randomized Phase II Trial.

NCT03623646 | Completed Phase 2 DMC

• 1 other identifier: 18 VADS 06
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a phase II, multicenter, open-label study that has been designed to evaluate the efficacy and the safety of definitive Radiotherapy (RT) (70 Gy) delivered in combination with the anti-PD-L1 Durvalumab immunotherapy in patients with Human Papilloma Virus (HPV)-related oropharyngeal squamous cell carcinoma. In this phase II trial, patients will be assigned in one of the two treatment arms:

• Arm A (standard arm): Chemoradiotherapy arm
• Arm B (Experimental arm): Immunotherapy + Radiotherapy arm Total duration of treatment will be 6 months (at maximum in the experimental arm). Patients will be followed for a maximum of 2 years following the date of randomization.

Conditions

Oropharyngeal Squamous Cell Carcinoma

Keywords

Oropharyngeal Squamous Cell Carcinoma; Anti PD-L1; Durvalumab; Radiation therapy; Cisplatin; Human Papilloma Virus

Outcome Measures

Primary Outcomes (1)

• The rate of patients alive without progression at 12 months.

  12 months for each patient

Secondary Outcomes (5)

• Progression-free survival.

  24 months for each patient

• Overall survival.

  24 months for each patient

• Safety will be evaluated using National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.03.

  24 months for each patient

• Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30).

  24 months for each patient

• Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head & Neck 35 (EORTC QLQ-H&N35).

  24 months for each patient

Study Arms (2)

Arm A (standard arm): Chemoradiotherapy arm

OTHER

Drug: Chemoradiotherapy arm

Arm B (Experimental arm): Immunotherapy + Radiotherapy arm

EXPERIMENTAL

Drug: Immunotherapy + Radiotherapy arm

Interventions

Chemoradiotherapy arm DRUG

Radiation Therapy in combination with Chemotherapy (Cisplatin)

Arm A (standard arm): Chemoradiotherapy arm

Immunotherapy + Radiotherapy arm DRUG

Radiation Therapy in combination with Immunotherapy drug (Durvalumab)

Arm B (Experimental arm): Immunotherapy + Radiotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, histologically proven squamous cell carcinoma of oropharynx T1 N1-N2 or T2-T3 N0 to N2 (AJCC 2018)
• HPV positive status (positive staining for p16 in immunochemistry)
• Presence of at least one measurable lesion according to RECIST v1.1 criteria (longest diameter recorded ≥10 mm with CT scan)
• No prior anticancer therapy for OSCC
• Patient eligible for definitive radiochemotherapy
• Age ≥ 18 years
• WHO performance status \< 2 i.e. 0 or 1
• Body weight \>30kg
• Life expectancy more than 3 months
• 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
• 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
• Adequate Hemostasis laboratory data within 6 weeks prior to start of treatment: TP within the normal range
• 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
• 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
• Signed written informed consent

You may not qualify if:

• T1 N0, T1-T3 N3, T4 N0-N3, p16 + OSCC
• Previous treatment with another check-point inhibitor
• Other histologies : UCNT, p16- SCCHN, sino-nasal tumors
• 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)
• Metastatic disease
• Previous radiotherapy, except anterior strictly out of field radiotherapy, received for treatment of another primary tumor considered in remission in the past 5 years
• Participation in another therapeutic trial within the 30 days prior to entering this study
• Uncontrolled disease such as diabetes, hypertension, symptomatic congestive heart or pulmonary failure, renal or hepatic chronic diseases... (non-exhaustive list)
• 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
• 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)
• 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

Sponsors & Collaborators

• Institut Claudius Regaud: lead
• AstraZeneca: collaborator

Study Sites (2)

CHU Bordeaux

Bordeaux, France

Location

Institut Universitaire du Cancer Toulouse (IUCT-O)

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 9, 2018
• Study Start: March 15, 2019
• Primary Completion: February 26, 2022
• Study Completion: February 14, 2023
• Last Updated: August 8, 2025

Record last verified: 2025-07

Locations

FR (2)