Durvalumab for Oropharyngeal squamous cell carcinoma | Locoregionally advanced HPV-positive oropharyngeal squamous cell carcinoma (intermediate risk)

Inclusion criteria

• {"criterion_text":"- Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oropharynx (OSCC) which is locoregionally advanced, intermediate risk and nonmetastatic (M0) as defined by the following (UICC/AJCC 8th Edition staging): • T1-2 N1 (smoking ≥ 10 pack years); • T3 N0-N1 (smoking ≥ 10 pack years); • T1-3 N2 (any smoking hx)."}
• {"criterion_text":"- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires in the languages provided."}
• {"criterion_text":"- Patients must be accessible for treatment and follow-up."}
• {"criterion_text":"- In accordance with CCTG policy, protocol treatment (cisplatin/RT or durvalumab) is to begin within 1 week of randomization."}
• {"criterion_text":"- The patient is not receiving anti-cancer therapy in a concurrent clinical study and the patient agrees not to participate in other clinical studies during their participation in this trial while on study treatment."}
• {"criterion_text":"- Adequate normal organ and marrow function as defined in the protocol (must be done within 14 days prior to randomization)."}
• {"criterion_text":"- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate."}
• {"criterion_text":"- Patients must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation including administration of radiotherapy, cisplatin and durvalumab as outlined in the protocol."}
• {"criterion_text":"- Human papillomavirus (HPV)-related as determined by positive p16 immunohistochemical staining on any tumour specimens. Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumour cells. Local testing is acceptable; testing will not be done centrally in real-time."}
• {"criterion_text":"- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix I) and a body weight of > 30 kg."}
• {"criterion_text":"- Must be ≥ 18 years of age."}
• {"criterion_text":"- The following radiological investigations must be done within 8 weeks of randomization: • CT or MRI of the neck (with PET-CT and head imaging as indicated); • CT chest or x-ray, other radiology tests as clinically indicated."}
• {"criterion_text":"- Women/men of childbearing potential must have agreed to use a highly effective contraceptive method while on study. Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception during the study and for 3 months after taking the last dose of durvalumab or up to 6 months after the last dose of chemoradiotherapy. Men, who wish to become fathers in the future, should ask for advice regarding cryoconservation of their sperm prior to treatment."}
• {"criterion_text":"- Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation. The pregnancy test (urine or serum) is to be repeated/ renewed every month during protocol treatment, at the end of protocol treatment and for 3 months after taking the last dose of durvalumab or up to 6 months after the last dose of chemoradiotherapy."}
• {"criterion_text":"- Patient must consent to provision of, and investigator(s) must confirm location and commit to obtain a representation of formalin fixed paraffin block of non-cytology tissue samples."}
• {"criterion_text":"- Patient must consent to provision of samples of blood, saliva and oropharyngeal swab."}

Exclusion criteria

• {"criterion_text":"- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years."}
• {"criterion_text":"- History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction."}
• {"criterion_text":"- Current or prior use of immunosuppressive medication within 28 days of study entry, with the exceptions of intranasal and inhaled corticosteroids or systemic chronic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Corticosteroids used on study for anti-emetic purpose are allowed. Corticosteroids as premedication for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication) are allowed."}
• {"criterion_text":"- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. There are exceptions in the protocol."}
• {"criterion_text":"- Patients with active or uncontrolled intercurrent illness including, but not limited to: • cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia); • active peptic ulcer disease or gastritis; • active bleeding diatheses; • psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent; • known history of previous clinical diagnosis of tuberculosis; • known active human immunodeficiency virus infection (positive HIV 1/2 antibodies). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible; • known active hepatitis B infection (positive HBV surface antigen (HBsAg). • known active hepatitis C infection."}
• {"criterion_text":"- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline CT scan."}
• {"criterion_text":"- Receipt of live attenuated vaccination (examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization."}
• {"criterion_text":"- Pregnant or lactating women."}
• {"criterion_text":"- Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy."}
• {"criterion_text":"- Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol."}
• {"criterion_text":"- Current history of other non-OSCC malignancies of the head and neck."}
• {"criterion_text":"- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an anti-CTLA4, including tremelimumab."}
• {"criterion_text":"- Any previous cisplatin or carboplatin chemotherapy."}
• {"criterion_text":"- Any previous induction chemotherapy for current SCCHN."}
• {"criterion_text":"- Any previous surgical treatment of the current cancer (except for a diagnostic biopsy) and no major surgery within 28 days prior to randomization."}
• {"criterion_text":"- Any previous radiation to the head and neck region that would result in overlap of fields for the current study."}
• {"criterion_text":"- History of allergic or hypersensitivity reactions to any study drug or their excipients."}
• {"criterion_text":"- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome."}

Primary endpoints

• {"endpoint_text":"- Event-free survival (EFS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Loco Regional Control (LRC)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Distant Metastasis Free Survival (DMFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Toxicity","definition_or_measurement_approach":"Toxicity is described to be estimated and described for Arms A, B and C; schedule includes assessment of radiation related late toxicity at 3 months, 6 months and 1 year from the end of RT and PRO-CTCAE at baseline, last week of treatment, 3 months, 6 months and 12, 24 and 36 months from the end of RT."}
• {"endpoint_text":"- Quality of life","definition_or_measurement_approach":"Quality of life will be assessed as change in FACT-HN score from baseline to 36 months post-RT; cost effectiveness of the immunotherapy-based experimental treatment arm vs. standard RT and cisplatin will use the EQ-5D-5L."}

Other endpoints

• {"endpoint_text":"- Incidence of second cancer","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dysphagia: PSS-HN swallowing subscale and MDADI Global at 36 months from the end of RT","definition_or_measurement_approach":"Dysphagia measured using PSS-HN swallowing subscale and MDADI Global at 36 months post-RT."}
• {"endpoint_text":"- PRO-CTCAE baseline, last week of treatment, 3 months, 6 months and 12, 24 and 36 months from the end of RT","definition_or_measurement_approach":"Patient-reported outcomes using PRO-CTCAE collected at specified timepoints (baseline, last week of treatment, 3, 6, 12, 24, 36 months post-RT)."}
• {"endpoint_text":"- Radiation related late toxicity at 3 months, 6 months and 1 year from the end of RT","definition_or_measurement_approach":"Late radiation-related toxicity assessed at 3, 6 and 12 months post-RT."}
• {"endpoint_text":"- Cost effectiveness of the immunotherapy-based experimental treatment arm vs. the standard of RT and cisplatin using the EQ-5D-5L; Cost utility and lost productivity","definition_or_measurement_approach":"Health economic evaluation using EQ-5D-5L for cost-effectiveness; cost-utility and lost productivity analyses planned."}
• {"endpoint_text":"- Biobanking","definition_or_measurement_approach":"Collection and storage of biological samples (formalin fixed paraffin block of non-cytology tissue samples, blood, saliva and oropharyngeal swab) for analysis/biobanking."}

Belgium

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

21-03-2024

Processing Time Days

21

Number Of Sites

5

Number Of Participants

13

Italy

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

22-03-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

01-04-2024

Processing Time Days

32

Number Of Sites

3

Number Of Participants

11

Primary sponsor

Full Name

European Organisation For Research And Treatment Of Cancer

Organisation Type

Patient organisation/association

Country Of Registered Address

Belgium

Third parties

• {"country":"Canada","full_name":"Queen's University","duties_or_roles":"Biobanking and samples analysis","organisation_type":"Educational Institution"}
• {"country":"Luxembourg","full_name":"Luxembourg Institute Of Health","duties_or_roles":"Samples storage, processing and shipment to Canada","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Durvalumab secondary packaging, labelling and supply","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"University Of Massachusetts Chan Medical School","duties_or_roles":"Central Radiotherapy Review and images banking","organisation_type":"Educational Institution"}