Clinical trial NCT02319044: Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck
Keywords: Head and neck cancer; SCCHN
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2014-12-18
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Maximum age (years): 96
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 after treatment with a platinum containing regimen for recurrent/metastatic disease.

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.

Eligibility criteria: Inclusion Criteria:

* 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;
* 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.

Exclusion Criteria:

* 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;
* 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

Primary outcomes:
measure: Objective Response Rate at 6 Months
timeFrame: After 6 months
measure: Objective Response Rate at 12 Months
timeFrame: After 12 months
Secondary outcomes:
measure: Best Objective Response
timeFrame: After 12 months
measure: Duration of Response - Participants Remaining in Response
timeFrame: After 12 months
measure: Time to Response
timeFrame: After 12 months
measure: Time to Onset of Response From First Dose
timeFrame: After 12 months
measure: Disease Control Rate (DCR)
timeFrame: After 6 months
measure: Disease Control Rate (DCR)
timeFrame: After 12 months
measure: Progression-free Survival (PFS)
timeFrame: After 6 months
measure: Progression-free Survival (PFS)
timeFrame: After 12 months
measure: Overall Survival
timeFrame: After 12 months
measure: Quality of Life
timeFrame: After 12 months
measure: Duration of Response
timeFrame: After 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Yuma
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
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state: Arkansas
city: Downey
country: United States
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state: California
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
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state: California
city: Long Beach
country: United States
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state: California
city: Los Angeles
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city: Augusta
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city: Evanston
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city: Baltimore
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city: Detroit
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state: New Hampshire
city: Bronx
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city: New York
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state: New York
city: Stony Brook
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state: New York
city: Durham
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state: North Carolina
city: Winston-Salem
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state: North Carolina
city: Portland
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city: Austin
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city: Morgantown
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state: West Virginia
city: Milwaukee
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city: Adelaide
country: Australia
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city: Darlinghurst
country: Australia
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city: Tweed Heads
country: Australia
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city: Brussels
country: Belgium
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city: Charleroi
country: Belgium
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city: Kortrijk
country: Belgium
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city: Leuven
country: Belgium
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city: Namur
country: Belgium
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city: Calgary
country: Canada
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state: Alberta
city: Moncton
country: Canada
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state: New Brunswick
city: London
country: Canada
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state: Ontario
city: Ottawa
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
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state: Quebec
city: Olomouc
country: Czechia
facility: Research Site
city: Zlin
country: Czechia
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Brest
country: France
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city: Dijon
country: France
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city: Le Mans
country: France
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city: Lille cedex
country: France
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city: Lorient cedex
country: France
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city: Lyon Cedex 08
country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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city: Strasbourg Cedex
country: France
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city: Toulouse Cedex 9
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Batumi
country: Georgia
facility: Research Site
city: Batumi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
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city: Tbilisi
country: Georgia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Halle
country: Germany
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city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Györ
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Gerona
country: Spain
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city: Granada
country: Spain
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city: Jaén
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Marbella (Málaga)
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com
name: Magdalena Wrona
role: STUDY_DIRECTOR
affiliation: Princess Margaret Hospital in Toronto, Ontario
name: Lillian Siu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.