Carcinoma, Squamous Cell of Head and NeckPhase 1CLOVERNCT03509012
Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors
A Phase 1 study testing Durvalumab, Tremelimumab and Cisplatin (dose level 4) in people with Carcinoma, Squamous Cell of Head and Neck and Carcinoma, Non-Small-Cell Lung, run by AstraZeneca at 16 sites in 5 countries.
Trial summary
This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
- What is being tested?
- Durvalumab, Tremelimumab and Cisplatin (dose level 4)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 16 sitesin 5 countries
- Study dates
- 2 May 2018to 8 Jan 2025
- Phase
- Phase 1
- 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 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- World Health Organization (WHO)/ECOG performance status of 0 or 1
- Body weight >30 kg at enrollment and treatment assignment
- At least 1 measurable lesion, not previously irradiated
- No prior exposure to immune-mediated therapy (including therapeutic anticancer vaccines)
- For patients with oropharyngeal HNSCC HPV status has to be known
Who cannot join
- Patients with simultaneous primary malignancies or bilateral tumors
- Active or prior documented autoimmune or inflammatory disorders
- Brain metastases or spinal cord compression
- Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies)
- Has a paraneoplastic syndrome (PNS) of autoimmune nature
- HNSCC cohort: Head and neck cancer that does not include unresectable, locally advanced cancer of oral cavity, larynx, oropharynx or hypopharynx. HNSCC of unknown primary are also excluded
- NSCLC and SCLC cohort: Mixed SCLC and NSCLC histology
- SCLC cohort: Extensive-stage SCLC
Trial locations and contacts
16 sites in 5 countries.
16 sites in 5 countries
South Korea4 sites
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Taiwan4 sites
Research Site
Taichung, 40705
Research Site
Taipei, 10002
Research Site
Taipei, 112
Research Site
Taoyuan City, 333
United States3 sites
Research Site
Aurora, Colorado, 80045
Research Site
Houston, Texas, 77090
Research Site
Tucson, Arizona, 85719
Spain3 sites
Research Site
Badalona, 08916
Research Site
Madrid, 28007
Research Site
Málaga, 29010
About this study
Official title: A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors
Read the detailed description
This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).
- Conditions
- Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
- Being tested
- Durvalumab, Tremelimumab, Cisplatin (dose level 4), Cisplatin (dose level 3), Carboplatin (dose level 1)
- Keywords
- Durvalumab, Chemotherapy, Radiotherapy, HNSCC, NSCLC, SCLC, locally-advanced, limited stage, first line
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
IV (intravenous)
TremelimumabDrug
IV
Cisplatin (dose level 4)Drug
IV
Cisplatin (dose level 3)Drug
IV
Carboplatin (dose level 1)Drug
IV
Carboplatin (dose level 2)Drug
IV
Etoposide (dose level 1)Drug
IV
Etoposide (dose level 2)Drug
IV
PaclitaxelDrug
IV
PemetrexedDrug
IV
External beam radiation (dose level 1)Radiation
radiation therapy
External beam radiation (dose level 2)Radiation
radiation therapy
External beam radiation (hyperfractionated)Radiation
radiation therapy
Cisplatin (dose level 1)Drug
IV
Cisplatin (dose level 2)Drug
IV
External beam radiation (standard)Radiation
radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| HNSCC Arm 1 | Experimental | Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC) Receives: Drug: Durvalumab; Drug: Cisplatin (dose level 4); Radiation: External beam radiation (dose level 1) |
| NSCLC Arm 1 | Experimental | Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC) Receives: Drug: Durvalumab; Drug: Etoposide (dose level 1); Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 1) |
| NSCLC Arm 2 | Experimental | Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC) Receives: Drug: Durvalumab; Drug: Carboplatin (dose level 1); Drug: Paclitaxel; Radiation: External beam radiation (dose level 2) |
| NSCLC Arm 3 | Experimental | Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed Receives: Drug: Durvalumab; Drug: Carboplatin (dose level 2); Drug: Pemetrexed; Radiation: External beam radiation (dose level 2); Drug: Cisplatin (dose level 2) |
| SCLC Arm 1 | Experimental | Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Receives: Drug: Durvalumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (standard) |
| SCLC Arm 2 | Experimental | Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Receives: Drug: Durvalumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (hyperfractionated) |
| SCLC Arm 3 | Experimental | Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable. Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (standard) |
| SCLC Arm 4 | Experimental | Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable. Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: Cisplatin (dose level 3); Drug: Carboplatin (dose level 2); Drug: Etoposide (dose level 2); Radiation: External beam radiation (hyperfractionated) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with Dose Limiting Toxicities (DLTs)
Measured: From first dose of durvalumab until 28 days after completion of radiation therapy
Number of subjects with Adverse Events (AEs)
Measured: From first dose of durvalumab up to 90 days after the last dose of study treatment
Secondary outcomes (7)
Progression-free survival (PFS)
Measured: From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years.
Overall Survival (OS)
Measured: From first dose until death due to any cause through study completion, up to 4 years
Objective response rate (ORR)
Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Measured: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Best objective response (BoR)
The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression.
Measured: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Duration of response (DoR)
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Measured: From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Disease control rate (DCR)
Measured: From first dose until disease progression, at 18 weeks and 48 weeks.
Disease-free survival (DFS)
Measured: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2018
- Study start2 May 2018
- Primary completion31 Dec 2020
- Study completion8 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Squamous Cell of Head and NeckStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03509012
- Sponsor's protocol ID
- D933BC00001
- Other IDs
- 2017-002242-77, 2017
- Acronym
- CLOVER
- Status last verified
- Jan 2025
- First submitted
- 12 Mar 2018
- Last updated
- 14 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
- ClinicalTrials.gov ID
- NCT03509012
- Acronym / sponsor ID
- CLOVER / D933BC00001
- Conditions
- Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
- Keywords
- Durvalumab, Chemotherapy, Radiotherapy, HNSCC, NSCLC, SCLC, locally-advanced, limited stage
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 2 May 2018 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 26 Apr 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 an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors
Detailed description
This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| HNSCC Arm 1 | Experimental | Drug: Durvalumab, Drug: Cisplatin (dose level 4), Radiation: External beam radiation (dose level 1)Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC) |
| NSCLC Arm 1 | Experimental | Drug: Durvalumab, Drug: Etoposide (dose level 1), Radiation: External beam radiation (dose level 2), Drug: Cisplatin (dose level 1)Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC) |
| NSCLC Arm 2 | Experimental | Drug: Durvalumab, Drug: Carboplatin (dose level 1), Drug: Paclitaxel, Radiation: External beam radiation (dose level 2)Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC) |
| NSCLC Arm 3 | Experimental | Drug: Durvalumab, Drug: Carboplatin (dose level 2), Drug: Pemetrexed, Radiation: External beam radiation (dose level 2), Drug: Cisplatin (dose level 2)Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed |
| SCLC Arm 1 | Experimental | Drug: Durvalumab, Drug: Cisplatin (dose level 3), Drug: Carboplatin (dose level 2), Drug: Etoposide (dose level 2), Radiation: External beam radiation (standard)Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin |
| SCLC Arm 2 | Experimental | Drug: Durvalumab, Drug: Cisplatin (dose level 3), Drug: Carboplatin (dose level 2), Drug: Etoposide (dose level 2), Radiation: External beam radiation (hyperfractionated)Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin |
| SCLC Arm 3 | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Drug: Cisplatin (dose level 3), Drug: Carboplatin (dose level 2), Drug: Etoposide (dose level 2), Radiation: External beam radiation (standard)Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable. |
| SCLC Arm 4 | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Drug: Cisplatin (dose level 3), Drug: Carboplatin (dose level 2), Drug: Etoposide (dose level 2), Radiation: External beam radiation (hyperfractionated)Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable. |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- World Health Organization (WHO)/ECOG performance status of 0 or 1
- Body weight >30 kg at enrollment and treatment assignment
- At least 1 measurable lesion, not previously irradiated
- No prior exposure to immune-mediated therapy (including therapeutic anticancer vaccines)
- For patients with oropharyngeal HNSCC HPV status has to be known
Key exclusion criteria (8 listed)
- Patients with simultaneous primary malignancies or bilateral tumors
- Active or prior documented autoimmune or inflammatory disorders
- Brain metastases or spinal cord compression
- Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies)
- Has a paraneoplastic syndrome (PNS) of autoimmune nature
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: MEDI4736IV (intravenous) | Drug | HNSCC Arm 1, NSCLC Arm 1, NSCLC Arm 2, NSCLC Arm 3, SCLC Arm 1, SCLC Arm 2, SCLC Arm 3, SCLC Arm 4 |
| TremelimumabIV | Drug | SCLC Arm 3, SCLC Arm 4 |
| Cisplatin (dose level 4)IV | Drug | HNSCC Arm 1 |
| Cisplatin (dose level 3)IV | Drug | SCLC Arm 1, SCLC Arm 2, SCLC Arm 3, SCLC Arm 4 |
| Carboplatin (dose level 1)IV | Drug | NSCLC Arm 2 |
| Carboplatin (dose level 2)IV | Drug | NSCLC Arm 3, SCLC Arm 1, SCLC Arm 2, SCLC Arm 3, SCLC Arm 4 |
| Etoposide (dose level 1)IV | Drug | NSCLC Arm 1 |
| Etoposide (dose level 2)IV | Drug | SCLC Arm 1, SCLC Arm 2, SCLC Arm 3, SCLC Arm 4 |
| PaclitaxelIV | Drug | NSCLC Arm 2 |
| PemetrexedIV | Drug | NSCLC Arm 3 |
| External beam radiation (dose level 1)radiation therapy | Radiation | HNSCC Arm 1 |
| External beam radiation (dose level 2)radiation therapy | Radiation | NSCLC Arm 1, NSCLC Arm 2, NSCLC Arm 3 |
| External beam radiation (hyperfractionated)radiation therapy | Radiation | SCLC Arm 2, SCLC Arm 4 |
| Cisplatin (dose level 1)IV | Drug | NSCLC Arm 1 |
| Cisplatin (dose level 2)IV | Drug | NSCLC Arm 3 |
| External beam radiation (standard)radiation therapy | Radiation | SCLC Arm 1, SCLC Arm 3 |
Primary outcome
Number of subjects with Dose Limiting Toxicities (DLTs)
Time frame: From first dose of durvalumab until 28 days after completion of radiation therapy
Number of subjects with Adverse Events (AEs)
Time frame: From first dose of durvalumab up to 90 days after the last dose of study treatment
7 secondary outcomes
Progression-free survival (PFS)
Time frame: From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years.
Overall Survival (OS)
Time frame: From first dose until death due to any cause through study completion, up to 4 years
Objective response rate (ORR)
Time frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Best objective response (BoR)
Time frame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Duration of response (DoR)
Time frame: From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Disease control rate (DCR)
Time frame: From first dose until disease progression, at 18 weeks and 48 weeks.
Disease-free survival (DFS)
Time frame: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 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 14 Jan 2025.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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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.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Durvalumab, Tremelimumab and Cisplatin (dose level 4) in people with Carcinoma, Squamous Cell of Head and Neck and Carcinoma, Non-Small-Cell Lung, run by AstraZeneca at 16 sites in 5 countries.
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 5 inclusion and 8 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 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in South Korea, Taiwan, United States, Spain, Japan. 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 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.
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?
Number of subjects with Dose Limiting Toxicities (DLTs) (time frame: From first dose of durvalumab until 28 days after completion of radiation therapy). 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 14 Jan 2025.