Oral Cavity Squamous Cell CarcinomaPhase 1/2DUTRELASCONCT03784066
Durvalumab With or Without Tremelimumab in Resectable Locally Advanced Squamous Cell Carcinoma of the Oral Cavity
A Phase 1/2 study testing Durvalumab and Durvalumab + Tremelimumab in people with Oral Cavity Squamous Cell Carcinoma, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Cavity Squamous Cell Carcinoma
- What is being tested?
- Durvalumab and Durvalumab + Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteBelgium
- Study dates
- 27 Aug 2018to 24 Mar 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Resectable locally advanced oral cavity SCC stage IV
- Newly diagnosed disease
- Age ≥18 years at the time of screening
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
- No active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix
- No prior chemotherapy, radiotherapy or targeted therapy including PD-1, PD-L1 or CTLA-4 antibodies for SCCHN, including durvalumab or tremelimumab
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- Availability of blood samples for Translational research
- Negative pregnancy test
- Normal organ function
- No participation in another interventional clinical trial in the preceding 30 days prior to randomization
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations
- Body weight > 30 kg
Who cannot join
- Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck
- Receipt of other treatments for cancer within 30 days prior to first dose of study treatment
- Previous radiotherapy in the head and neck region
- Previous systemic therapy for SCCHN
- Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP.
- History of allogeneic organ transplantation
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- Active or prior documented autoimmune or inflammatory
- Uncontrolled intercurrent illness
- Active relevant second malignancy during the last five years
- Mean QT interval corrected for heart rate ≥470 ms
- History of active primary immunodeficiency
- Active infection Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
- Female patients of childbearing potential who are pregnant or breast-
- Known allergy or hypersensitivity to IP or any IP excipient
- Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP
- Metastatic disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Durvalumab (MEDI4736) Plus Tremelimumab in Resectable, Locally Advanced Squamous Cell Carcinoma of the Oral Cavity: a Window of Opportunity Study
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.
Read the detailed description
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.
- Conditions
- Oral Cavity Squamous Cell Carcinoma
- Being tested
- Durvalumab, Durvalumab + Tremelimumab
- Keywords
- squamous cell carcinoma
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
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.
Durvalumab + TremelimumabCombination product
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.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Durvalumab Receives: Drug: Durvalumab |
| B | Active comparator | Durvalumab + Tremelimumab Receives: Combination Product: Durvalumab + Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of biological response in tumor tissue by means of difference in CD8 lymfocyte infiltration density
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.
Measured: The first biopsy will be harvested as part of the diagnostic screening procedures between day 28 and 14 before surgery. The second biopsy will be harvest from the resection specimen on day 0. IP will be given exactly 14 days before surgery.
Secondary outcomes (5)
Imaging
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.
Measured: After 14 days of treatment, prior to surgery
68Ga-CXCR-4 PET/MR (optional)
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.
Measured: After 14 days of treatment, prior to surgery
Locoregional control in days
Patient follow up according to standard of care will include locoregional control, measured in days.
Measured: Up to 2 years after surgery
Time to treatment failure in days
Patient follow up according to standard of care will include time to treatment failure, measured in days.
Measured: Up to 2 years after surgery
Overall survival in days
Overall survival will be measured in days
Measured: Up to 5 years after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2018
- Study start27 Aug 2018
- Primary completion24 Mar 2025 (estimated)
- Study completion24 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral Cavity Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, European Organisation for Research and Treatment of Cancer - EORTC, Flemish institute of biotechnology (VIB)
- Responsible party
- Sponsor
- Investigators
- Paul Clement, Prof., Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03784066
- Sponsor's protocol ID
- ESR-16-12192
- Other IDs
- 2017-000577-36, 2017
- Acronym
- DUTRELASCO
- Status last verified
- Jul 2024
- First submitted
- 31 Oct 2018
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durvalumab (MEDI4736) Plus Tremelimumab in Resectable, Locally Advanced Squamous Cell Carcinoma of the Oral Cavity: a Window of Opportunity Study
- ClinicalTrials.gov ID
- NCT03784066
- Acronym / sponsor ID
- DUTRELASCO / ESR-16-12192
- Conditions
- Oral Cavity Squamous Cell Carcinoma
- Keywords
- squamous cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- AstraZeneca, European Organisation for Research and Treatment of Cancer - EORTC, Flemish institute of biotechnology (VIB)
- Study start
- 27 Aug 2018 (actual)
- Primary completion
- 24 Mar 2025 (estimated)
- Study completion
- 24 Mar 2026 (estimated)
- First posted
- 21 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: DurvalumabDurvalumab |
| B | Active comparator | Combination Product: Durvalumab + TremelimumabDurvalumab + Tremelimumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Resectable locally advanced oral cavity SCC stage IV
- Newly diagnosed disease
- Age ≥18 years at the time of screening
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
- No active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix
Key exclusion criteria (17 listed)
- Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck
- Receipt of other treatments for cancer within 30 days prior to first dose of study treatment
- Previous radiotherapy in the head and neck region
- Previous systemic therapy for SCCHN
- Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAll 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. | Drug | A |
| Durvalumab + TremelimumabAll 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. | Combination product | B |
Primary outcome
Evaluation of biological response in tumor tissue by means of difference in CD8 lymfocyte infiltration density
Time frame: The first biopsy will be harvested as part of the diagnostic screening procedures between day 28 and 14 before surgery. The second biopsy will be harvest from the resection specimen on day 0. IP will be given exactly 14 days before surgery.
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.
5 secondary outcomes
Imaging
Time frame: After 14 days of treatment, prior to surgery
68Ga-CXCR-4 PET/MR (optional)
Time frame: After 14 days of treatment, prior to surgery
Locoregional control in days
Time frame: Up to 2 years after surgery
Time to treatment failure in days
Time frame: Up to 2 years after surgery
Overall survival in days
Time frame: Up to 5 years after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Clement, Prof. principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Durvalumab and Durvalumab + Tremelimumab in people with Oral Cavity Squamous Cell Carcinoma, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of biological response in tumor tissue by means of difference in CD8 lymfocyte infiltration density (time frame: The first biopsy will be harvested as part of the diagnostic screening procedures between day 28 and 14 before surgery. The second biopsy will be harvest from the resection specimen on day 0. IP will be given exactly 14 days before surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024; AzTrials last refreshed its copy on 7 Nov 2026.