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

NCT03623646

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 18 VADS 06
  • NCT ID: NCT03623646

Conditions

  • Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Chemoradiotherapy armArm A (standard arm): Chemoradiotherapy arm
Immunotherapy + Radiotherapy armArm B (Experimental arm): Immunotherapy + Radiotherapy arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A (standard arm): Chemoradiotherapy armOther
  • Chemoradiotherapy arm
Arm B (Experimental arm): Immunotherapy + Radiotherapy armExperimental
  • Immunotherapy + Radiotherapy arm

Eligibility Criteria

        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, Cholesterolemia ≤ 7.30 mmol/L

         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) > 480 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The rate of patients alive without progression at 12 months.
Time Frame:12 months for each patient
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival.
Time Frame:24 months for each patient
Safety Issue:
Description:
Measure:Overall survival.
Time Frame:24 months for each patient
Safety Issue:
Description:
Measure:Safety will be evaluated using National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.03.
Time Frame:24 months for each patient
Safety Issue:
Description:
Measure: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).
Time Frame:24 months for each patient
Safety Issue:
Description:
Measure: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).
Time Frame:24 months for each patient
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Institut Claudius Regaud

Trial Keywords

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

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