resectable, locally advanced squamous cell carcinoma of the oral cavity
Conditions
Sponsors
University Hospitals Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =18 years at the time of screening • Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. • Histologically or cytologically confirmed resectable locally advanced stage IV SCC of the oral cavity. Staging will be performed according to 7th Edition of the AJCC/UICC Staging System. • No prior systemic therapy for SCCHN disease is allowed. • No prior radiation therapy in the head and neck is allowed • No active second malignancy during the last five years except non-melanomatous skin cancer or carcinoma in situ • Able and willing to give valid written consent to provide newly acquired tumor tissue for the purpose of the analyses defined in the protocol. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment • Body weight > 30 kg • Patients must have no prior exposure to immune-mediated therapy, including anti-CTLA-4,including tremelimumab anti-PD-1, anti–PD-L1including durvalumab, or anti–programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines. • Adequate organ and marrow function: o Adequate bone marrow function demonstrated by neutrophils count = 1,500/mm3, platelet count = 100,000/mm3, Haemoglobin = 9.0 g/dL ? Adequate hepatic function: AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be = 5x ULN; bilirubin = 1.5 times upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician. o Adequate renal function as demonstrated by serum creatinine = 1.5 mg/dL (< 133 µmol/L) or calculated creatinine clearance = 50 ml/min as determined by CKD-EPI [51] – o Prothrombin time (PT) or international normalized ratio (INR) < or = 1.2 times (ULN) o Partial thromboplastin time (PTT) < or = 1.2 times ULN • Adequate cardiac function assessed by 12-lead ECG • Availability of blood samples for Translational research • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and 6 months beyond stop of treatment in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Females should not be pregnant or breast feeding. Males should not father a baby while on this study and 6 months beyond because the drugs in this study can affect an unborn baby. o Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments or if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution. o Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments and if they have luteinizing
Exclusion criteria
Exclusion criteria: • Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, salivary gland) • Receipt of: o any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment. o any previous radiation therapy in the head and neck o any previous systemic therapy for SCCHN o any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment. • Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP. The following are exceptions to this criterion unless otherwise indicated: o Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection) o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent o Steroids as pre-medication for hypersensitivity reactions (eg, CT scan pre-medication) and/or as anti-emetics for the SoC arm • History of allogeneic organ transplantation • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, Crohn’s disease] with the exception of a prior episode that has resolved; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: o Patients with vitiligo or alopecia o Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement o Psoriasis not requiring systemic treatment • 11. Uncontrolled intercurrent illness, including, but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness or social situations that would limit compliance with study requirements or substantially increase the risk of incurring AEs from IP • Active second malignancy during the last five years except for the following: non melanomatous skin cancer that has been surgically cured, non-invasive malignancies, such as carcinoma in situ. Other in situ carcinomas that have been adequately treated may be permitted. • Mean QT interval corrected for heart rate =470 ms • History of active primary immunodeficiency • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. • Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP. • Female patients of childbearing potential who are pregnant or breast-feeding or who are not willing t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the biological response in the tumor upon treatment with durvalumab, and in parallel, with combination of durvalumab and tremelimumab. ;Secondary Objective: The feasibility to use a 68 Ga-ligand CXCR4 immunotracer PET-MR to measure immune response in the tumor Safety analysis of addition of durvalumab with or without tremelimumab to standard of care treatment LRC, TTF and OS after treatment, combining durvalumab (arm 1) or durvalumab + tremelimumab (arm 2) with SOC treatment (radiotherapy with or without chemotherapy) PD-L1 testing before and after single dose of durvalumab and/or tremelimumab ;Primary end point(s): The primary objective is to evaluate the biological response by means of CD8 infiltration density in the tumor upon treatment with durvalumab, and in parallel, with combination of durvalumab and tremelimumab on the biopsy (before treatment) and on the resection specimen (after 1 cycle of treatment).;Timepoint(s) of evaluation of this end point: CD8 infiltration density will be assessed by immunohistochemistry on the biopsy and on the resection specimen. A >1.5-fold increase of CD8 infiltration density would be considered a treatment success. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 imaging:Response after 14 days of treatment, prior to surgery, evaluated by 68Ga-CXCR-4 PET/MR. RECIST v1.1 will be used to compare MRI images (as part of the 68Ga-CXCR-4 PET/MR) to preoperative imaging. 2 Locoregional control, time to treatment failure and overall survival->will be evaluated up to 2 years after surgery 3 safety analysis 4 endpoints involve the evaluation of outcome prediction by several biomarkers;Timepoint(s) of evaluation of this end point: 1 after 14 days of treatment, prior to surgery 2will be evaluated up to 2 years after surgery 3 if the first 3 patients in arm 1 do not develop unexpected severe toxicity related to concurrent treatment with cisplatin and radiotherapy, new patients are allowed to be treated according to the protocol | — |
Countries
Belgium
Contacts
Public ContactPaul Clement
University Hospitals Leuven
Outcome results
None listed