Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Durvalumab

Tremelimumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

All patients will be treated with postoperative radiotherapy (66 Gy in standard fractionation).

In case of positive section margins or extracapsular extension, 3 cycles of cisplatin 100 mg/msq on days 1, 22, and 43 will be added to standard fractionation radiotherapy (66 Gy).

Durvalumab monotherapy (1500 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 6 cycles postoperative.

All patients will be treated with postoperative radiotherapy (66 Gy in standard fractionation).

In case of positive section margins or extracapsular extension, 3 cycles of cisplatin 100 mg/msq on days 1, 22, and 43 will be added to standard fractionation radiotherapy (66 Gy).

Durvalumab + Tremelimumab combination therapy: Tremelimumab (75 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 3 cycles postoperative, Durvalumab (1500 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 6 cycles postoperative.

Durvalumab + Tremelimumab

Paul Clement, Prof.

This is a randomized, open-label, prospective, pilot phase I/II study with focus on translational research and on the evaluation of the biological changes that are observed in sequential tumor tissue acquisition in patients with newly diagnosed advanced (stage IV) oral cavity SCC. Patients are treated with Durvalumab (arm A) or Durvalumab + Tremelimumab (arm B) after biopsy-confirmed diagnosis of locally advanced resectable SCCHN of the oral cavity. After surgery, the standard of care treatment is radiotherapy, and, depending on risk assessment concurrent cisplatin. Patients will be treated with Durvalumab (arm A) or Durvalumab and Tremelimumab (arm B) during six additional cycles, starting from day one of the postoperative radiotherapy.

Durvalumab has shown activity in squamous cell carcinoma of the head and neck. Locally advanced resectable cancers of this type represent a challenge, as the majority of these patients still die from this disease in spite of surgery, radio- and chemotherapy.

Checkpoint inhibitors have recently proven to prolong life in recurrent/metastatic SCCHN, and several new molecules are currently tested in clinical trials in this indication, including PD-1, PD-L1, and CTLA-4 antibodies, either as single agent or in combination. These compounds might represent a valuable treatment for SCCHN patients in the adjuvant setting, given the favorable toxicity profile. Combination of Durvalumab (PD-L1 inhibition) and Tremelimumab (CTLA-4 inhibition) is currently tested in recurrent/metastatic head and neck cancer, and compared to Durvalumab as single agent, and to standard of care chemotherapy.

In this study both options, i.e. durvalumab as a single agent or Durvalumab in combination with Tremelimumab, will be tested in a randomized fashion. Randomization would be used to reduce selection bias, in a non-comparative study. Newly diagnosed patients with SCCHN of the oral cavity, will be treated with a single dose of Durvalumab with or without Tremelimumab two weeks before scheduled surgery.

When patients are first diagnosed with a resectable oral SCC, a biopsy is taken to confirm the diagnosis, and surgery is planned. This standard practice thus involves sequential tissue harvesting, both at the time of biopsy as well as the final resection specimen, making it possible to observe hallmarks of immune response when patients are treated once with Durvalumab with or without Tremelimumab after confirmation of the diagnosis on biopsy, but before surgery.

The primary objective is to evaluate the biological response in the tumor upon treatment with Durvalumab, and in parallel, with combination of Durvalumab and Tremelimumab.

Durvalumab With or Without Tremelimumab in Resectable Locally Advanced Squamous Cell Carcinoma of the Oral Cavity

Durvalumab (MEDI4736) Plus Tremelimumab in Resectable, Locally Advanced Squamous Cell Carcinoma of the Oral Cavity: a Window of Opportunity Study

Difference in CD8 infiltration density will be evaluated on Formalin-Fixed Paraffin-Embedded sections. Measurements will be done both visually by trained pathologists and quantitative on immunofluorescence panel.

RECIST v1.1 will be used to compare MRI images to preoperative imaging in order to non-invasively detect potential radiological changes induced by the investigated drug.

RECIST v1.1 will be used to compare MRI images (as part of the 68Ga-CXCR-4 PET/MR) to preoperative imaging in order to:

* assess the correlation of metabolic 68Ga-CXCR-4 PET/MR with immune response in the tumor
* identify an imaging technique able to detect immunologic activity that could serve as an imaging biomarker to select early those patients that may benefit from durvalumab with or without tremelimumab.

Patient follow up according to standard of care will include locoregional control, measured in days.

Patient follow up according to standard of care will include time to treatment failure, measured in days.

Overall survival will be measured in days

AstraZeneca

European Organisation for Research and Treatment of Cancer - EORTC

Vlaams Instituut voor Biotechnologie (VIB)

Universitaire Ziekenhuizen KU Leuven

Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.

Durvalumab: 1.5g Q4W plus Tremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.

durvalumab + tremelimumab

Bhumsuk Kim, Ph.D.

To understand efficacy of Durvalumab(MEDI4736)+ Tremelimumab in Metastatic/relapsed pulmonary sarcomatoid carcinoma

This is a phase II multi-center, open-label study to evaluate efficacy and safety of durvalumab + tremelimumab combination treatment in patients with pulmonary sarcomatoid carcinoma

Pulmonary sarcomatoid_MEDI4736+Treme

Phase II Study of Durvalumab + Tremelimumab in Pulmonary Sarcomatoid Carcinoma

According to modified RECIST1.1, The duration from the first date of treatment to the date of death from any cause or follow-up

The percentage of patients who have not experienced disease progression or death from any cause within 12 months from the start of treatment.

The duration from the first date of treatment to the date of death from any cause or follow-up

The number of patients with treatment-related AE as assessed by NCI CTCAE version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Durvalumab With or Without Tremelimumab in Resectable Locally Advanced Squamous Cell Carcinoma of the Oral Cavity	NCT03784066	Oral Cavity Squ...	Durvalumab Durvalumab + Tr...	18 Years -	Universitaire Ziekenhuizen KU Leuven
Pulmonary sarcomatoid_MEDI4736+Treme	NCT03022500	Durvalumab + Tr...	durvalumab + tr...	20 Years -	Seoul National University Hospital

Spots Global Cancer Trial Database for durvalumab + tremelimumab