DUTRELASCO trial (DUrvalumab with or without Tremelimumab in REsectable Locally Advanced Squamous cell Carcinoma of the Oral cavity)

Phase 1

• Conditions: resectable, locally advanced squamous cell carcinoma of the oral cavity; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000577-36-BE
• Lead Sponsor: niversity Hospitals Leuven

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-19
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 20

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:
oAdequate 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.
oAdequate 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] –
oProthrombin time (PT) or international normalized ratio (INR) < or = 1.2 times (ULN)
oPartial 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.
oWomen =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

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:
oany radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment.
oany previous radiation therapy in the head and neck
oany previous systemic therapy for SCCHN
oany 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:
oIntranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
oSystemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
oSteroids 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:
oPatients with vitiligo or alopecia
oPatients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
oPsoriasis 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 H

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified