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AzTrials

Recurrent/Metastatic Squamous Cell Carcinoma of Head & NeckPhase 2NCT02319044

Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck

A Phase 2 study testing MEDI4736, Tremelimumab and MEDI4736 + Tremelimumab in people with Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck, run by AstraZeneca at 125 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine the efficacy and safety of investigational medical products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of the head and neck who have progressed during or… Read more about this study

Who is it for?
Ages 18 to 96 years
What is being tested?
MEDI4736, Tremelimumab and MEDI4736 + Tremelimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
267 participants
Where
125 sitesin 15 countries
Study dates
15 Apr 2015to 6 Jul 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 96 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years;
  • Written informed consent obtained from the patient/legal representative;
  • Histologically confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
  • Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
  • Confirmed PD-L1-negative SCCHN by Ventana SP263;
  • WHO/ECOG performance status of 0 or 1;
Show all 9Show fewer
  • At least 1 measurable lesion at baseline;
  • No prior exposure to immune-mediated therapy;
  • Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.

Who cannot join

  • Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck;
  • Received more than 1 regimen for recurrent or metastatic disease
  • Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment;
  • Receipt of any investigational anticancer therapy within 28 days or 5 half-lives;
  • Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment;
  • Major surgical procedure within 28 days prior to the first dose of Investigational Product;
Show all 21Show fewer
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion;
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product;
  • History of allogeneic organ transplantation;
  • Active or prior documented autoimmune or inflammatory disorders;
  • Uncontrolled intercurrent illness;
  • another primary malignancy
  • Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis;
  • History of active primary immunodeficiency;
  • Known history of previous tuberculosis;
  • Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product;
  • Pregnant or breast-feeding female patients;
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
  • Known allergy or hypersensitivity to Investigational Product.
  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results

Trial locations and contacts

125 sites in 15 countries.

125 sites in 15 countries

United States43 sites
  • Research Site

    Ann Arbor, Michigan, 48109

  • Research Site

    Arlington, Texas, 76012

  • Research Site

    Atlanta, Georgia, 30322

  • Research Site

    Augusta, Georgia, 30912

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    Austin, Texas, 78701

  • Research Site

    Baltimore, Maryland, 21201

  • Research Site

    Baltimore, Maryland, 21204

  • Research Site

    Bethlehem, Pennsylvania, 18015

  • Research Site

    Birmingham, Alabama, 35294

  • Research Site

    Boston, Massachusetts, 02215

  • Research Site

    Charleston, South Carolina, 29425

  • Research Site

    Chicago, Illinois, 60637

  • Research Site

    Dallas, Texas, 75230

  • Research Site

    Detroit, Michigan, 48201

  • Research Site

    Downey, California, 90241

  • Research Site

    Duarte, California, 91010-3012

  • Research Site

    Durham, North Carolina, 27705

  • Research Site

    Evanston, Illinois, 60201

  • Research Site

    Knoxville, Tennessee, 37909

  • Research Site

    La Jolla, California, 92093

  • Research Site

    Lebanon, New Hampshire, 03756

  • Research Site

    Lexington, Kentucky, 40536-0001

  • Research Site

    Little Rock, Arkansas, 72205

  • Research Site

    Long Beach, California, 90813

  • Research Site

    Los Angeles, California, 90033

  • Research Site

    Los Angeles, California, 90095

  • Research Site

    Macon, Georgia, 31201

  • Research Site

    Milwaukee, Wisconsin, 53226

  • Research Site

    Morgantown, West Virginia, 26506

  • Research Site

    Nashville, Tennessee, 37232

  • Research Site

    New York, New York, 10032

  • Research Site

    Pittsburgh, Pennsylvania, 15232

  • Research Site

    Portland, Oregon, 97239

  • Research Site

    Rochester, Minnesota, 55905-0001

  • Research Site

    San Francisco, California, 94115

  • Research Site

    Southfield, Michigan, 48075

  • Research Site

    St Louis, Missouri, 63110

  • Research Site

    Stony Brook, New York, 11794

  • Research Site

    Tampa, Florida, 33612

  • Research Site

    The Bronx, New York, 10467

  • Research Site

    Winston-Salem, North Carolina, 27157

  • Research Site

    Yuma, Arizona, 85364

Other trials in United States

France16 sites
  • Research Site

    Angers, 49933

  • Research Site

    Bordeaux, 33604

  • Research Site

    Brest, 29229

  • Research Site

    Dijon, 21079

  • Research Site

    Le Mans, 72000

  • Research Site

    Lille, 59020

  • Research Site

    Lorient, 56322

  • Research Site

    Lyon, 69373

  • Research Site

    Montpellier, 34298

  • Research Site

    Nice, 6189

  • Research Site

    Rouen, 76038

  • Research Site

    Saint-Brieuc, 22015

  • Research Site

    Saint-Grégoire, 35768

  • Research Site

    Strasbourg, 67085

  • Research Site

    Toulouse, 31059

  • Research Site

    Villejuif, 94805

Other trials in France

Spain15 sites
  • Research Site

    Barakaldo, 48903

  • Research Site

    Barcelona, 08035

  • Research Site

    Barcelona, 08036

  • Research Site

    Barcelona, 08907

  • Research Site

    Girona, 17007

  • Research Site

    Granada, 18014

  • Research Site

    Jaén, 23007

  • Research Site

    Madrid, 28041

  • Research Site

    Madrid, 28046

  • Research Site

    Madrid, 28050

  • Research Site

    Málaga, 29010

  • Research Site

    Marbella (Málaga), 29600

  • Research Site

    Valencia, 46014

  • Research Site

    Valencia, 46026

  • Research Site

    Zaragoza, 50009

Other trials in Spain

Hungary8 sites
  • Research Site

    Budapest, 1077

  • Research Site

    Budapest, 1083

  • Research Site

    Budapest, 1122

  • Research Site

    Győr, 9024

  • Research Site

    Gyula, 5700

  • Research Site

    Kecskemét, 6000

  • Research Site

    Miskolc, 3526

  • Research Site

    Zalaegerszeg, 8900

Other trials in Hungary

Canada7 sites
  • Research Site

    Calgary, Alberta, T2N 2T9

  • Research Site

    London, Ontario, N6A 4L6

  • Research Site

    Moncton, New Brunswick, E1C 6Z8

  • Research Site

    Montreal, Quebec, H4A 3J1

  • Research Site

    Ottawa, Ontario, K1H 8L6

  • Research Site

    Sherbrooke, Quebec, J1H 5N4

  • Research Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Germany6 sites
  • Research Site

    Berlin, 12203

  • Research Site

    Halle, 06120

  • Research Site

    Hanover, 30625

  • Research Site

    Heidelberg, 69120

  • Research Site

    Leipzig, 04103

  • Research Site

    München, 81377

Other trials in Germany

United Kingdom6 sites
  • Research Site

    Aberdeen, AB25 2ZN

  • Research Site

    Birmingham, B15 2TH

  • Research Site

    Glasgow, G12 0YN

  • Research Site

    London, E1 1BB

  • Research Site

    Manchester, M20 4BX

  • Research Site

    Metropolitan Borough of Wirral, CH63 4JY

Other trials in United Kingdom

Belgium5 sites
  • Research Site

    Brussels, 1090

  • Research Site

    Charleroi, 6000

  • Research Site

    Kortrijk, 8500

  • Research Site

    Leuven, 3000

  • Research Site

    Namur, 5000

Other trials in Belgium

Georgia5 sites
  • Research Site

    Batumi, 6010

  • Research Site

    Batumi, 6400

  • Research Site

    Tbilisi, 0144

  • Research Site

    Tbilisi, 0177

  • Research Site

    Tbilisi, 0179

Other trials in Georgia

Australia3 sites
  • Research Site

    Adelaide, 5000

  • Research Site

    Darlinghurst, 2010

  • Research Site

    Tweed Heads, 2485

Other trials in Australia

Israel3 sites
  • Research Site

    Haifa, 31096

  • Research Site

    Petah Tikva, 4941492

  • Research Site

    Tel HaShomer, 52621

Other trials in Israel

South Korea3 sites
  • Research Site

    Daegu, 42601

  • Research Site

    Goyang-si, 10408

  • Research Site

    Suwon, 16247

Other trials in South Korea

Czechia2 sites
  • Research Site

    Olomouc, 775 20

  • Research Site

    Zlín, 762 75

Other trials in Czechia

Malaysia2 sites
  • Research Site

    Kuala Lumpur, 59100

  • Research Site

    Kuching, 93586

Other trials in Malaysia

Taiwan1 site
  • Research Site

    Taipei, 10449

Other trials in Taiwan

About this study

Official title: A Phase II, Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination With Tremelimumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

The purpose of this study is to determine the efficacy and safety of investigational medical products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of the head and neck who have progressed during or after treatment with a platinum containing regimen for recurrent/metastatic disease.

Read the detailed description

This is a randomized, open-label, multi-center, global, Phase II study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy and tremelimumab monotherapy in the treatment of patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease, that must have contained a platinum agent.

Patients will be randomized in a stratified manner according to prognostic factors, including human papillomavirus (HPV) status and smoking status to achieve a balance between treatments for each of the factors. Patients will be randomized in a 1:1:2 fashion to receive MEDI4736 monotherapy, tremelimumab monotherapy, or MEDI4736 + tremelimumab combination.

All treatments will be administered beginning on Day 0 for 12 months or until confirmed progression of disease; unless, in the Investigator's opinion, the patient continues to receive benefit from the treatment), initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Patients with confirmed progression of disease who, in the Investigator's opinion, continue to receive benefit from their assigned investigational product and who meet the criteria for treatment in the setting of progression of disease may continue to receive their assigned investigational product treatment for a maximum of 12 months after consultation with the Sponsor and at the Investigator's discretion. The monotherapy arms (tremelimumab and MEDI4736) should be discontinued if there is confirmed progression of disease following a previous response in target lesions (complete response or partial response).

Tumor assessments will be performed using computed tomography or magnetic resonance imaging. Efficacy for all patients will be assessed by objective tumor assessments every 8 weeks (q8w) for the first 48 weeks (relative to the date of the first infusion) then q12w in patients who have disease control after 12 months until confirmed objective disease progression.

Following completion or discontinuation of treatment, patients will enter a follow-up period.

Being tested
MEDI4736, Tremelimumab, MEDI4736 + Tremelimumab
Keywords
Head and neck cancer; SCCHN
Medical subject headings
Recurrence, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MEDI4736Drug

    MEDI4736 monotherapy

  • TremelimumabDrug

    Tremelimumab monotherapy

  • MEDI4736 + TremelimumabDrug

    MEDI4736 + Tremelimumab combination therapy

Study groups in NCT02319044
Study groupRoleWhat they receive
MEDI4736ExperimentalMEDI4736 monotherapy
Receives: Drug: MEDI4736
TremelimumabExperimentalTremelimumab monotherapy
Receives: Drug: Tremelimumab
MEDI4736 + TremelimumabExperimentalMEDI4736 + Tremelimumab combination therapy
Receives: Drug: MEDI4736 + Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate at 6 Months

    Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses

    Measured: After 6 months

  2. Objective Response Rate at 12 Months

    Objective response rate (per RECIST 1.1 as assessed by blinded independent central review [BICR]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors [RECIST] 1.1. criteria are: Complete response [CR] = disappearance of all target lesions since baseline; and partial response [PR] = at least a 30% decrease in the sum of the diameters of target lesions.

    Measured: After 12 months

Secondary outcomes (11)
  1. Best Objective Response

    The best response a patient has had during their time in the study

    Measured: After 12 months

  2. Duration of Response - Participants Remaining in Response

    Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.

    Measured: After 12 months

  3. Time to Response

    Time to response in patients with objective response based on BICR assessments according to RECIST 1.1

    Measured: After 12 months

  4. Time to Onset of Response From First Dose

    Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1

    Measured: After 12 months

  5. Disease Control Rate (DCR)

    Disease control rate (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.

    Measured: After 6 months

  6. Disease Control Rate (DCR)

    Disease control rate (DCR) at 12 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.

    Measured: After 12 months

  7. Progression-free Survival (PFS)

    Progression status at 6 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.

    Measured: After 6 months

  8. Progression-free Survival (PFS)

    Progression status at 12 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.

    Measured: After 12 months

  9. Overall Survival

    Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status or patients who were lost to follow-up.

    Measured: After 12 months

  10. Quality of Life

    Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: -The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. -Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35. The symptom and QoL/function improvement rate was defined as the number (%) of patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10 or EORTC QLQ-C30 scales) in that symptom/function from baseline. For QLQ-H\&N35A a minimum clinically meaningful change was defined as a change in the score from baseline of >10 for scales/items

    Measured: After 12 months

  11. Duration of Response

    Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of Complete response/Partial response (which was subsequently confirmed) until the date of progression, death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off (per RECIST v1.1 as assessed by BICR).

    Measured: After 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2014 (estimated)
  2. Study start15 Apr 2015
  3. Primary completion26 Sep 2016
  4. Study completion6 Jul 2020

Resources

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
Masking
None (open label)
Enrolment
267 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02319044
Sponsor's protocol ID
D4193C00003
Status last verified
Sep 2020
First submitted
12 Dec 2014
Last updated
29 Sep 2020
Data monitoring committee
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

Publications

  • Siu LL, Even C, Mesia R, Remenar E, Daste A, Delord JP, Krauss J, Saba NF, Nabell L, Ready NE, Brana I, Kotecki N, Zandberg DP, Gilbert J, Mehanna H, Bonomi M, Jarkowski A, Melillo G, Armstrong JM, Wildsmith S, Fayette J. Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):195-203. doi: 10.1001/jamaoncol.2018.4628.

    PubMed 30383184

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MEDI4736, Tremelimumab and MEDI4736 + Tremelimumab in people with Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck, run by AstraZeneca at 125 sites in 15 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 9 inclusion and 21 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 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 125 sites in United States, France, Spain, Hungary, Canada and 10 more countries. 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?

Yes. Results are posted in the registry (first posted 19 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate at 6 Months (time frame: After 6 months). 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?

On the ClinicalTrials.gov record for NCT02319044, which also lists 1 linked publication.

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 29 Sep 2020.

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