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

NCT ID: NCT02319044

Last Updated: 2020-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-15
• Study Completion Date: 2020-07-06

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.

Conditions

Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MEDI4736

MEDI4736 monotherapy

Group Type: EXPERIMENTAL

MEDI4736

Intervention Type: DRUG

MEDI4736 monotherapy

Tremelimumab

Tremelimumab monotherapy

Group Type: EXPERIMENTAL

Tremelimumab

Intervention Type: DRUG

Tremelimumab monotherapy

MEDI4736 + Tremelimumab

MEDI4736 + Tremelimumab combination therapy

Group Type: EXPERIMENTAL

MEDI4736 + Tremelimumab

Intervention Type: DRUG

MEDI4736 + Tremelimumab combination therapy

Interventions

MEDI4736

MEDI4736 monotherapy

Intervention Type: DRUG

Tremelimumab

Tremelimumab monotherapy

Intervention Type: DRUG

MEDI4736 + Tremelimumab

MEDI4736 + Tremelimumab combination therapy

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 96 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Magdalena Wrona

Role: STUDY_DIRECTOR

Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com

Lillian Siu, MD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Hospital in Toronto, Ontario

Locations

Research Site

Birmingham, Alabama, United States

Research Site

Yuma, Arizona, United States

Research Site

Little Rock, Arkansas, United States

Research Site

Downey, California, United States

Research Site

Duarte, California, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Macon, Georgia, United States

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Chicago, Illinois, United States

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Evanston, Illinois, United States

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Lexington, Kentucky, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Southfield, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Lebanon, New Hampshire, United States

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New York, New York, United States

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Stony Brook, New York, United States

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The Bronx, New York, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Portland, Oregon, United States

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Bethlehem, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

Research Site

Morgantown, West Virginia, United States

Research Site

Milwaukee, Wisconsin, United States

Research Site

Adelaide, , Australia

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Darlinghurst, , Australia

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Tweed Heads, , Australia

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Brussels, , Belgium

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Charleroi, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Namur, , Belgium

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Calgary, Alberta, Canada

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Moncton, New Brunswick, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Olomouc, , Czechia

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Zlín, , Czechia

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Angers, , France

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Bordeaux, , France

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Brest, , France

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Dijon, , France

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Le Mans, , France

Research Site

Lille, , France

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Lorient, , France

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Lyon, , France

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Montpellier, , France

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Nice, , France

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Rouen, , France

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Saint-Brieuc, , France

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Saint-Grégoire, , France

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Strasbourg, , France

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Toulouse, , France

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Villejuif, , France

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Batumi, , Georgia

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Batumi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Berlin, , Germany

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Halle, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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München, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Győr, , Hungary

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Gyula, , Hungary

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Kecskemét, , Hungary

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Miskolc, , Hungary

Research Site

Zalaegerszeg, , Hungary

Research Site

Haifa, , Israel

Research Site

Petah Tikva, , Israel

Research Site

Tel Litwinsky, , Israel

Research Site

Kuala Lumpur, , Malaysia

Research Site

Kuching, , Malaysia

Research Site

Daegu, , South Korea

Research Site

Goyang-si, , South Korea

Research Site

Suwon, , South Korea

Research Site

Barakaldo, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Girona, , Spain

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Granada, , Spain

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Jaén, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Marbella (Málaga), , Spain

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Málaga, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Taipei, , Taiwan

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Aberdeen, , United Kingdom

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Birmingham, , United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

Research Site

Metropolitan Borough of Wirral, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Czechia; France; Georgia; Germany; Hungary; Israel; Malaysia; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30383184 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3110&filename=Redacted%20CONDOR%20Protocol%2020Sept17.pdf

Redacted Protocol

Other Identifiers

D4193C00003

Identifier Type: -

Identifier Source: org_study_id