Study of First Line MEDI4736 with or without Tremelimumab Versus standard of care chemotherapy in Recurrent or Metastatic Head and Neck cancer

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2015-003589-10-GR
• Date of registration: 03/11/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Study of First Line MEDI4736 with or without Tremelimumab Versus standard of care chemotherapy in Recurrent or Metastatic Head and Neck cancer
• Scientific title: A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination with Tremelimumab versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients - KESTREL
• Date of first enrolment: 21/12/2015
• Target sample size: 760
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003589-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Cetuximab + Platinum (Cisplatin or Carboplatin) + 5FU; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Japan, Korea, Democratic People's Republic of, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age =18 years at the time of screening
2. Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) ).
3. A fresh tumor biopsy for the purpose of screening or an available archival
tumor sample.
4. No prior systemic therapy for recurrent/metastatic disease. Systemic therapy given as part of multimodality treatment for locally advanced or locally recurrent disease is allowed.
5. World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment
6. No prior exposure to immune-mediated therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 456
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 304

Exclusion criteria:
1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous
histologies (eg, nasopharynx or salivary gland)
2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn’s disease], diverticulitis


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have not received prior systemic chemotherapy.
MedDRA version: 21.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: tremelimumab
Product Code: MEDI1123
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tremelimumab
CAS Number: 745013-59-6
Current Sponsor code: MEDI1123
Other descriptive name: MEDI1123
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Erbitux
Product Name: cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Cetuximab
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Carboplatin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: 5-fluorouracil (5FU)
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: FLUOROURACIL
CAS Number: 54-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Cisplatin
CAS Number: 15663-27-1
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Assessments for survival must be made every 3 months following treatment discontinuation and/or upon disease progression.

Secondary Objective: Assess efficacy of MEDI4736 monotherapy compared to SoC in terms of OS, PFS, ORR, DoR, BoR, TTR, TFST, TSST, APF6, APF12, PFS2, OS12, OS18 & OS24

Assess efficacy of MEDI4736 +tremelimumab combination therapy compared to SoC in terms of OS, PFS, ORR, DoR, BoR, TTR, TFST, TSST, APF6, APF12, PFS2, OS12, OS18 & OS24

Assess efficacy of MEDI4736+ tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS, ORR & OS

Assess disease-related symptoms and health-related quality of life in patients treated with MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC using the EORTC 30-item Core QLQ-C30 & QLQ H&N35 modules

Assess PK of MEDI4736 + tremelimumab combination therapy & MEDI4736 monotherapy

Investigate immunogenicity of MEDI4736 & tremelimumab

Assess safety & tolerability profile of MEDI4736 + tremelimumab combination therapy & MEDI4736 monotherapy compared to SoC in the first-line setting for treatment of SCCHN

Main Objective: To assess the efficacy of MEDI4736 monotherapy versus SoC (EXTREME) in PD-L1 TC/IC high subgroup in terms of OS.

Primary end point(s): OS in the PD-L1 TC/IC subgroup

Secondary Outcome(s)

Secondary end point(s): OS in low risk of early mortality (EM) subgroup, ctDNA TMB high subgroup and all-comers

OS12, OS18, OS24 in the PD-L1 TC/IC subgroup, low risk of EM subgroup, and ctDNA TMB high subgroup and all-comers

PFS, ORR, APF6 and APF12 in the PD-L1 TC/IC subgroup, low risk of EM subgroup, ctDNA TMB high subgroup and all-comers using site investigator assessments according to RECIST 1.1

DoR, BoR and TTR using site investigator assessments according to RECIST 1.1 in the PD-L1 TC/IC subgroup and all-comers

PFS2 using local standard clinical practice in the PD-L1 TC/IC subgroup and all-comers

TFST and TSST in the PD-L1 TC/IC subgroup and all-comers

EORTC QLQ-C30 - global health QoL, functioning (physical) and symptoms (fatigue) in the PD-L1 TC/IC subgroup and all-comers

EORTC QLQ-H&N35 - symptoms (pain, swallowing) in the PD-L1 TC/IC subgroup and all-comers

Changes in World Health Organization/Eastern Cooperative Oncology Group performance status in the PD-L1 TC/IC subgroup and all-comers

Concentration of MEDI4736 and tremelimumab in blood and PK parameters, such as peak concentration and trough

Presence of ADAs for MEDI4736 and tremelimumab

Timepoint(s) of evaluation of this end point: PFS - At baseline, after that every 6 weeks for the first 24 weeks relative to the date of randomization, and then every 8 weeks until progression.

Assessments for survival must be made every 3 months following treatment discontinuation and/or upon disease progression.

EORTC QLQ-C30- Every 8 weeks (±3 days) relative to the date of Cycle 1 Day 1

EORTC QLQ-H&N35 - Every 4 weeks (±3 days) relative to the date of Cycle 1 Day 1

WHO/ECOG - Every cycle until PD

MEDI4736 and tremelimumab PK - Cycles 1, 2, 4 and 7

ADAs for MEDI4736 and tremelimumab - Cycles 1, 4 and 7

Secondary ID(s)

2015-003589-10-SK

NCT02551159

D419LC00001

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 15/12/2015
Contact: