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

Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02319044
• Other study ID #: D4193C00003
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2015
• Est. completion date: July 6, 2020

Study information

• Verified date: September 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: July 6, 2020
• Est. primary completion date: September 26, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 96 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• MEDI4736
MEDI4736 monotherapy
• Tremelimumab
Tremelimumab monotherapy
• MEDI4736 + Tremelimumab
MEDI4736 + Tremelimumab combination therapy

Locations

Country	Name	City	State
Australia	Research Site	Adelaide
Australia	Research Site	Darlinghurst
Australia	Research Site	Tweed Heads
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Canada	Research Site	Calgary	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Olomouc
Czechia	Research Site	Zlin
France	Research Site	Angers
France	Research Site	Bordeaux
France	Research Site	Brest
France	Research Site	Dijon
France	Research Site	Le Mans
France	Research Site	Lille cedex
France	Research Site	Lorient cedex
France	Research Site	Lyon Cedex 08
France	Research Site	Montpellier
France	Research Site	Nice
France	Research Site	Rouen
France	Research Site	Saint Brieuc
France	Research Site	St Grégoire
France	Research Site	Strasbourg Cedex
France	Research Site	Toulouse Cedex 9
France	Research Site	Villejuif Cedex
Georgia	Research Site	Batumi
Georgia	Research Site	Batumi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Germany	Research Site	Berlin
Germany	Research Site	Halle
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Leipzig
Germany	Research Site	München
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Györ
Hungary	Research Site	Gyula
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Hungary	Research Site	Zalaegerszeg
Israel	Research Site	Haifa
Israel	Research Site	Petach-Tikva
Israel	Research Site	Tel Hashomer
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Suwon
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Spain	Research Site	Barakaldo
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Gerona
Spain	Research Site	Granada
Spain	Research Site	Jaén
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Marbella (Málaga)
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Taiwan	Research Site	Taipei
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Wirral
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Arlington	Texas
United States	Research Site	Atlanta	Georgia
United States	Research Site	Augusta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Downey	California
United States	Research Site	Duarte	California
United States	Research Site	Durham	North Carolina
United States	Research Site	Evanston	Illinois
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Jolla	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Macon	Georgia
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Francisco	California
United States	Research Site	Southfield	Michigan
United States	Research Site	Stony Brook	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Yuma	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	PRA Health Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Georgia,  Germany,  Hungary,  Israel,  Korea, Republic of,  Malaysia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	After 6 months
Primary	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.	After 12 months
Secondary	Best Objective Response	The best response a patient has had during their time in the study	After 12 months
Secondary	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.	After 12 months
Secondary	Time to Response	Time to response in patients with objective response based on BICR assessments according to RECIST 1.1	After 12 months
Secondary	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	After 12 months
Secondary	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.	After 6 months
Secondary	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.	After 12 months
Secondary	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.	After 6 months
Secondary	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.	After 12 months
Secondary	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.	After 12 months
Secondary	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	After 12 months
Secondary	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).	After 12 months

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