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: 4 December 2023
• Main ID: EUCTR2015-003589-10-ES
• Date of registration: 29/12/2015
• 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: 30/12/2015
• Target sample size: 628
• 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: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age > o = 18 years at the time of screening
2. Documented evidence of 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 chemotherapy for recurrent or metastatic disease
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 376
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 252

Exclusion criteria:
1. Received any systemic therapy for recurrent or metastatic SCCHN
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: 18.1 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: 745013-19-6
Current Sponsor code: MEDI1123
Other descriptive name: MEDI1123
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

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)

Secondary Objective: To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS, ORR, DoR, APF12, PFS2, OS, and OS24

To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS, ORR, PFS2, OS, and OS24

To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS, ORR, and OS

To assess disease-related symptoms and health-related quality of life in patients treated with MEDI4736 + tremelimumab combination therapy compared to SoC using the EORTC 30-item Core QLQ-C30 version 3 and the 35-item Head and Neck QLQ H&N35 module

To assess the PK of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy

To investigate the immunogenicity of MEDI4736 and tremelimumab

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

Main Objective: To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS and OS

Primary end point(s): Co-primary: PFS using the Investigator?s assessments according to RECIST 1.1, and OS

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.

Secondary Outcome(s)

Secondary end point(s): PFS in patients with PD-L1-negative SCCHN using Investigator assessments according to RECIST 1.1
OS in patients with PD-L1-negative SCCHN
ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice
OS24
EORTC QLQ-C30
EORTC QLQ-H&N35
Changes in World Health Organization/Eastern Cooperative Oncology Group performance status
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental 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.

EORTC QLQ-C30- Every 4 weeks for the first 12 weeks relative to the date of randomization, then every 8 weeks thereafter.

EORTC QLQ-H&N35 - Every 2 weeks for the first 12 weeks relative to the date of randomization, then every 4 weeks thereafter.

Secondary ID(s)

D419LC00001

2015-003589-10-SK

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 04/12/2015
Contact:

Results

• Results available: Yes
• Date Posted: 05/02/2022
• Date Completed: 06/07/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003589-10/results