Squamous Cell Carcinoma of the Head and NeckPhase 2DURTRE-RADNCT03624231
Feasibility & Efficacy of Durvalumab+Tremelimumab+RT and Durvalumab+RT in Non-resect. Locally Advanced HPVnegativ HNSCC
A Phase 2 study testing Durvalumab, Tremelimumab and Radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Ulrich Keilholz at 3 sites in Germany.
Trial summary
Phase II trial evaluating to assess the feasibility and efficacy as first-line therapy for patients with non-resectable locally advanced HPV negative HNSCC of Durvalumab a PDL1-Inhibitor plus Tremelimumab a CTLA-4- Inhibitor in combination with radiotherapy and Durvalumab in combination with radiotherapy as first-line… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Durvalumab, Tremelimumab and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesGermany
- Study dates
- 15 Aug 2018to 17 Aug 2023
- Phase
- Phase 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
- Patients with locally advanced histopathologically confirmed HNSCC not candidate for primary surgical treatment
- No distant metastasis (M0)
- Tumor tissue available for central testing Patient with HPV/p16 negative disease (≤70% positively stained cells) as determined by central testing
- Adequate normal organ and marrow function
- Measurable tumor according to RECIST
- Patients must be expected to complete the treatment.
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- Age > 18 years at time of study entry
- Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry and be willing to use adequate contraceptive measurements as described in the protocol
- Non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use adequate contraceptive measurements as described in the protocol section 6.5.4
Who cannot join
- Participation in another clinical study with an investigational product during the last 3 months
- Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, EGFR inhibitors or radiotherapy).
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
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- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone History of primary immunodeficiency
- History of allogeneic organ transplant
- History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of hypersensitivity to durvalumab and/or tremelimumab or any excipient
- 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, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- 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.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control as described in the protocol from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
- Distant metastasis
- Patients who are institutionalised by official order
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
- Receipt of live attenuated vaccination within 30 days prior to study entry step 2 or within 30 days of receiving durvalumab or tremelimumab
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Vivantes Klinikum Neukölln
Berlin, 12351
Charité Comprehensive Cancer Center
Berlin, 13187
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45147
About this study
Official title: Ph II Trial to Assess Feasibility+Efficacy of Treatment w Durva+Treme+Radiation and Treatment w Durva+Radiation as First-line Therapy for Patients w Non-resectable Locally Advanced HPV-HNSCC- a Comparision With a Historical Control Group
Phase II trial evaluating to assess the feasibility and efficacy as first-line therapy for patients with non-resectable locally advanced HPV negative HNSCC of Durvalumab a PDL1-Inhibitor plus Tremelimumab a CTLA-4- Inhibitor in combination with radiotherapy and Durvalumab in combination with radiotherapy as first-line therapy.
2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization.
Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor in one of the two arms (Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.
Read the detailed description
The primary objective is to explore the feasibility and efficacy in terms of treatment discontinuation due to toxicity and in terms of 1-year progression free survival of a PDL1-Inhibitor plus a CTLA-4 Inhibitor in combination with radiotherapy and a PDL1-Inhibitor in combination with radiotherapy as first-line therapy for patients with non-resectable locally advanced HNSCC in the poor prognostic subgroup.
Secondary objectives are to investigate the benefit of the addition of a CTLA-4 Inhibitor and/or a PDL1-Inhibitor to radiotherapy in terms of overall progression free survival, overall survival and to investigate the approach in terms of safety, chronic toxicity and quality of life.
- Being tested
- Durvalumab, Tremelimumab, Radiotherapy
- Keywords
- Squamous Cell Carcinoma of the Head and Neck
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab (1500 mg) starting on week 1 to complete a total of 12 months
TremelimumabDrug
Tremelimumab (75 mg) for up to 4 doses/cycles
RadiotherapyRadiation
Radiotherapy with 35 fractions (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - stopped after interims analyses | Experimental | Patients in arm 1 will receive a single dose of durvalumab of 1500 mg administered on day 1, 14 days prior to initiation of the radiotherapy.
Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14. On week 5, 9, 13 and 17 patients will receive durvalumab (1500 mg) and tremelimumab (75 mg) for up to 4 doses/cycles and then continue 1500 mg durvalumab q4w starting on week 21 to complete a total of 12 months of therapy (overall 9 single doses durvalumab including the initial dose on day 1). Receives: Drug: Durvalumab; Drug: Tremelimumab; Radiation: Radiotherapy |
| Arm 2 | Experimental | Patients in arm 2 will receive durvalumab (1500 mg) q4w starting on day 1. Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14.
Overall patients will receive treatment with durvalumab mono up to a total of 12 months (up to 13 doses in total). Receives: Drug: Durvalumab; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy- 1-year progression free survival (PFS)
1-year progression free survival (PFS) depicted as the 1-year in-field-progression-free survival and 1-year distant metastasis free survival
Measured: 1 year
Feasibility - Number of treatment discontinuations due to toxicity
number of treatment discontinuations due to toxicity
Measured: During treatment
Secondary outcomes (4)
Overall Survival (OS)
defined as the time from patient inclusion to the date of death or date of last follow-up news
Measured: From date of randomization until the date of death, assessed up to 3 years
Safety - Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
defined as event possibly related to study treatment and fulfills the criteria using CTCAE Version 4.03
Measured: From date of randomization until the date of study assessed up to 3 years
Chronic toxicity -Number of participants with treatment-related adverse Events Lasting longer than 3 months as assessed by CTCAE v4.03 and/or RTOG/EORTC Late Radiation Morbidity Scoring Schema
defined as event lasting longer than 3 months and possibly related to study treatment and fulfills the criteria using CTCAE Version 4.03 and/or and/or RTOG/EORTC Late Radiation Morbidity Scoring Schema
Measured: From date of randomization until the date of study assessed up to 3 years
Quality of life (QoL) - measured by EORTC QLQ-H&N35 and EORTC QLQ-C30)
defined as assessment for evaluation of medical and psychosocial interventions
Measured: From date of randomization until the date of study assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start15 Aug 2018
- Primary completion17 Aug 2023
- Study completion17 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization. Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor one of the two arms Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ulrich Keilholz
- Sponsor type
- University, hospital or other
- Collaborators
- Charite University, Berlin, Germany, AstraZeneca
- Responsible party
- Sponsor-investigator, Ulrich Keilholz, Charite University, Berlin, Germany
- Investigators
- Ulrich Keilholz, MD, Study chair, Charité Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03624231
- Sponsor's protocol ID
- DURTRE-RAD
- Acronym
- DURTRE-RAD
- Status last verified
- Aug 2023
- First submitted
- 5 Dec 2017
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ph II Trial to Assess Feasibility+Efficacy of Treatment w Durva+Treme+Radiation and Treatment w Durva+Radiation as First-line Therapy for Patients w Non-resectable Locally Advanced HPV-HNSCC- a Comparision With a Historical Control Group
- ClinicalTrials.gov ID
- NCT03624231
- Acronym / sponsor ID
- DURTRE-RAD / DURTRE-RAD
- Keywords
- Squamous Cell Carcinoma of the Head and Neck
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Ulrich KeilholzUniversity, hospital or other
- Collaborators
- Charite University, Berlin, Germany, AstraZeneca
- Study start
- 15 Aug 2018 (actual)
- Primary completion
- 17 Aug 2023 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 10 Aug 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.
Phase II trial evaluating to assess the feasibility and efficacy as first-line therapy for patients with non-resectable locally advanced HPV negative HNSCC of Durvalumab a PDL1-Inhibitor plus Tremelimumab a CTLA-4- Inhibitor in combination with radiotherapy and Durvalumab in combination with radiotherapy as first-line therapy.
2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization.
Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor in one of the two arms (Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.
Detailed description
The primary objective is to explore the feasibility and efficacy in terms of treatment discontinuation due to toxicity and in terms of 1-year progression free survival of a PDL1-Inhibitor plus a CTLA-4 Inhibitor in combination with radiotherapy and a PDL1-Inhibitor in combination with radiotherapy as first-line therapy for patients with non-resectable locally advanced HNSCC in the poor prognostic subgroup.
Secondary objectives are to investigate the benefit of the addition of a CTLA-4 Inhibitor and/or a PDL1-Inhibitor to radiotherapy in terms of overall progression free survival, overall survival and to investigate the approach in terms of safety, chronic toxicity and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization. Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor one of the two arms Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - stopped after interims analyses | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Radiation: RadiotherapyPatients in arm 1 will receive a single dose of durvalumab of 1500 mg administered on day 1, 14 days prior to initiation of the radiotherapy. Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14. On week 5, 9, 13 and 17 patients will receive durvalumab (1500 mg) and tremelimumab (75 mg) for up to 4 doses/cycles and then continue 1500 mg durvalumab q4w starting on week 21 to complete a total of 12 months of therapy (overall 9 single doses durvalumab including the initial dose on day 1). |
| Arm 2 | Experimental | Drug: Durvalumab, Radiation: RadiotherapyPatients in arm 2 will receive durvalumab (1500 mg) q4w starting on day 1. Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14. Overall patients will receive treatment with durvalumab mono up to a total of 12 months (up to 13 doses in total). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with locally advanced histopathologically confirmed HNSCC not candidate for primary surgical treatment
- No distant metastasis (M0)
- Tumor tissue available for central testing Patient with HPV/p16 negative disease (≤70% positively stained cells) as determined by central testing
- Adequate normal organ and marrow function
- Measurable tumor according to RECIST
Key exclusion criteria (23 listed)
- Participation in another clinical study with an investigational product during the last 3 months
- Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, EGFR inhibitors or radiotherapy).
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- History of allogeneic organ transplant
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 |
|---|---|---|
| DurvalumabAlso: MEDI4736Durvalumab (1500 mg) starting on week 1 to complete a total of 12 months | Drug | Arm 1 - stopped after interims analyses, Arm 2 |
| TremelimumabTremelimumab (75 mg) for up to 4 doses/cycles | Drug | Arm 1 - stopped after interims analyses |
| RadiotherapyRadiotherapy with 35 fractions (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) | Radiation | Arm 1 - stopped after interims analyses, Arm 2 |
Primary outcome
Efficacy- 1-year progression free survival (PFS)
Time frame: 1 year
1-year progression free survival (PFS) depicted as the 1-year in-field-progression-free survival and 1-year distant metastasis free survival
Feasibility - Number of treatment discontinuations due to toxicity
Time frame: During treatment
number of treatment discontinuations due to toxicity
4 secondary outcomes
Overall Survival (OS)
Time frame: From date of randomization until the date of death, assessed up to 3 years
Safety - Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time frame: From date of randomization until the date of study assessed up to 3 years
Chronic toxicity -Number of participants with treatment-related adverse Events Lasting longer than 3 months as assessed by CTCAE v4.03 and/or RTOG/EORTC Late Radiation Morbidity Scoring Schema
Time frame: From date of randomization until the date of study assessed up to 3 years
Quality of life (QoL) - measured by EORTC QLQ-H&N35 and EORTC QLQ-C30)
Time frame: From date of randomization until the date of study assessed up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- 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.
Ulrich Keilholz, MD study chair
Charité Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab, Tremelimumab and Radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Ulrich Keilholz at 3 sites in Germany.
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 9 inclusion and 23 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: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy- 1-year progression free survival (PFS) (time frame: 1 year). The study lists 2 primary outcomes in all. 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 31 Aug 2023.