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Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers (PembroMetaRT)

Primary Purpose

Squamous Cell Carcinoma of Head and Neck

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Pembrolizumab

Loco-regional radiotherapy

Chemotherapy

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of Head and Neck focused on measuring Metastatic, Radiotherapy, pembrolizumab, Squamous Cell Carcinoma, Head and Neck, Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
Newly diagnosed histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) with histologically confirmed distant metastases at presentation (T1-4 N0-3 M1)
Eligible for treatment by pembrolizumab according to the European Marketing Authorization
Patient ≥18 years old
Performance status: 0-1 (WHO)
Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)
Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:
1. Absolute neutrophil count ≥1.5 × 10⁹/L
2. Platelet ≥100 × 10⁹/L
3. Hemoglobin ≥90 g/L
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted)
5. Bilirubin ≤1.5 × ULN.
6. Serum albumin ≥25 g/L
7. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)
8. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L.
Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration
Patients must be affiliated to a Social Security System (or equivalent)

Exclusion Criteria:

Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma
Prior radiotherapy in the head and neck region
Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent
Known Acquired Immune Deficiency Syndrome (AIDS)
Known currently active infection including hepatitis B or hepatitis C
Patient having received live attenuated vaccine within 28 days prior to enrolment
Pregnant or breast feeding woman
Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
Active immunodeficiency or ongoing immunosuppressive therapy
Active symptomatic interstitial lung disease
Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
Any social, personal, medical, geographic and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent
Prior organ transplantation including allogenic stem-cell transplantation
Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Person deprived of their liberty or under protective custody or guardianship
Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Radiotherapy added to systemic treatment

Systemic treatment

Arm Description

Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity. Loco-regional radiotherapy will start at D8 after the first administration of pembrolizumab (D1) with 54 Gy/18 fractions in the head and neck region. If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will start from cycle 3 or 4 of pembrolizumab (after radiotherapy administration) and will combine carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles

Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity. If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Secondary Outcome Measures

Overall survival (OS)

The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether the radiotherapy improves overall survival compared to standard of care.

Quality of life questionnaire - Core 30 (QLQ-C30)

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35)

The head & neck cancer module is a 35-item questionnaire designed for use among a wide range of patients with head & neck cancer, varying in disease stage and treatment modality. It includes 7 multi-item scales that assess pain (4 items), swallowing (4 items), senses (2 items), speech (3 items), social eating (4 items), social contact (5 items), and sexuality (2 items). There are also 11 single items. Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms. For all items and scales, high scores indicate more problems.

Objective response rate (ORR)

The Objective response rate is defined as the presence of a partial response (PR) or complete response (CR) observed at week 18. The investigator will evaluate the objective response using RECIST v1.1.

Loco-regional progression

Locoregional disease progression is defined as the time from randomization to the first documented locoregional progression evaluated by RECIST v1.1.

Distant progression

Distant progression is defined as the time from randomization to the first documented distant disease progression evaluated by RECIST v1.1.

Progression-free survival 2 (PFS2)

Progression-free survival 2 is defined as time from randomization to a second tumor progression (according to RECIST V1.1) on next-line treatment (given after a first progression) or death from any cause. Patients who did not have a progression after the initial treatment are counted as an event at the time of death if they died whatever the cause of death or are censored at the time of last news if they are alive. Patients who had a progression after the initial treatment are counted as an event when they progressed again under or after the treatment of the first progression (if they start a new treatment, i.e. a third treatment, they are also counted as an event) or when they died whatever the cause of death or they are censored at the time of last news if they are alive without new progression after the first progression.

Incidence of Treatment Adverse Events

The tolerance and safety will be evaluated by toxicity (acute [<1 months after the end of pembrolizumab] and late [≥1 month after the end of pembrolizumab]), assessed using the Common terminology criteria for adverse events version 5.0 (CTCAE v5.0).

Compliance to treatment

Compliance to treatment is defined by the difference on recieved study regimen compared to the planned study regimen.

Full Information

NCT ID

NCT04747054

First Posted

February 5, 2021

Last Updated

October 12, 2023

Sponsor

UNICANCER

Collaborators

GORTEC, National Cancer Institute, France

1. Study Identification

Unique Protocol Identification Number

NCT04747054

Brief Title

Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers

Acronym

PembroMetaRT

Official Title

Randomized Trial of Loco-regional Radiotherapy Added to Pembrolizumab Alone or With Chemotherapy Versus Systemic Treatment Alone for Patients With Newly Diagnosed Head and Neck Squamous Cell Carcinoma With Synchronous Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2021 (Actual)

Primary Completion Date

October 1, 2025 (Anticipated)

Study Completion Date

October 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNICANCER

Collaborators

GORTEC, National Cancer Institute, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head & neck cancers

Detailed Description

Comparative interventional prospective phase 3, randomised, open-label, multicentric trial comparing the combination of radiotherapy and pembrolizumab alone or with chemotherapy to systemic treatment as first line treatment of patients with newly diagnosed head and neck squamous cell carcinoma with synchronous metastases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Squamous Cell Carcinoma of Head and Neck

Keywords

Metastatic, Radiotherapy, pembrolizumab, Squamous Cell Carcinoma, Head and Neck, Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

148 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radiotherapy added to systemic treatment

Arm Type

Experimental

Arm Description

Arm Title

Systemic treatment

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

KEYTRUDA

Intervention Description

Pembrolizumab 200 mg every 3 weeks until disease progression (as confirmed according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)) or unacceptable toxicity. The treatment of pembrolizumab should not be delayed because of radiotherapy planning.

Intervention Type

Radiation

Intervention Name(s)

Loco-regional radiotherapy

Intervention Description

The loco-regional radiotherapy will start at D8 after the first administration of pembrolizumab (D1) (if delayed, RT should be started no later than three weeks after the first administration of pembrolizumab, i.e. before the second administration of pembrolizumab if possible), with 54 Gy/18 fractions in the head and neck region. The volume of RT will include only involved loco-regional tumor region and no prophylactic neck volume will be necessary.

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Intervention Description

If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles

Primary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Time Frame

From randomization to disease progression or death, up to 3 years.

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

Time Frame

From randomization to death from any cause, up to 5 years.

Title

Quality of life questionnaire - Core 30 (QLQ-C30)

Description

Time Frame

At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years

Title

Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35)

Description

Time Frame

At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years

Title

Objective response rate (ORR)

Description

Time Frame

At 18 weeks and 21 weeks

Title

Loco-regional progression

Description

Locoregional disease progression is defined as the time from randomization to the first documented locoregional progression evaluated by RECIST v1.1.

Time Frame

From randomization to loco-regional progression, up to 5 years.

Title

Distant progression

Description

Distant progression is defined as the time from randomization to the first documented distant disease progression evaluated by RECIST v1.1.

Time Frame

From randomization to distant progression, up to 5 years.

Title

Progression-free survival 2 (PFS2)

Description

Time Frame

Up to 5 years after randomization.

Title

Incidence of Treatment Adverse Events

Description

Time Frame

Throughout study completion, up to 5 years.

Title

Compliance to treatment

Description

Compliance to treatment is defined by the difference on recieved study regimen compared to the planned study regimen.

Time Frame

Throughout study treatment, up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent. Newly diagnosed histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) with confirmed distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion. Eligible for treatment by pembrolizumab according to the European Marketing Authorization Patient ≥18 years old Performance status: 0-1 (WHO) Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice) Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization: Absolute neutrophil count ≥1.5 × 10⁹/L Platelet ≥100 × 10⁹/L Hemoglobin ≥90 g/L Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) Bilirubin ≤1.5 × ULN. Serum albumin ≥25 g/L Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L. Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration Patients must be affiliated to a Social Security System (or equivalent) Exclusion Criteria: Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma Prior radiotherapy in the head and neck region Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent Known Acquired Immune Deficiency Syndrome (AIDS) Known currently active infection including hepatitis B or hepatitis C Patient having received live attenuated vaccine within 28 days prior to enrolment Pregnant or breast feeding woman Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment Active immunodeficiency or ongoing immunosuppressive therapy Active symptomatic interstitial lung disease Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial Any social, personal, medical, geographic and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent Prior organ transplantation including allogenic stem-cell transplantation Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study Person deprived of their liberty or under protective custody or guardianship Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

NICOLAS DE SOUSA CARVALHO

Phone

0171936709

n-de-sousa@unicancer.fr

First Name & Middle Initial & Last Name or Official Title & Degree

LAURE MONARD

Phone

01 73 79 73 09

l-monard@unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yungan TAO

Organizational Affiliation

Gustave Roussy, Cancer Campus, Grand Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut Sainte Catherine

City

Avignon

ZIP/Postal Code

84000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Benoit CALDERON, Dr

Facility Name

CHU Jean Minjoz

City

Besançon

ZIP/Postal Code

25030

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Salim BENHMIDA

Facility Name

CHU Bordeaux

City

Bordeaux

ZIP/Postal Code

33075

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amaury DASTE, Dr

Facility Name

Institut Bergonié

City

Bordeaux

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pauline GUILLON, Dr

Facility Name

Centre François Baclesse

City

Caen

ZIP/Postal Code

14076

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Juliette THARIAT, Dr

Facility Name

CH Carcassonne

City

Carcassonne

ZIP/Postal Code

1A810

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Samir HACENE, Dr

Facility Name

Centre Jean Perrin

City

Clermont-Ferrand

ZIP/Postal Code

63011

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hervé DEVAUD, Dr

Facility Name

Centre Georges François Leclerc

City

Dijon

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Noémie VULQUIN, Dr

Facility Name

Centre Guillaume le Conquérant

City

Le Havre

Country

France

Individual Site Status

Suspended

Facility Name

Centre Jean Bernard - Clinique Victor Hugo

City

Le Mans

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yoann POINTREAU, Dr

Facility Name

Centre Oscar Lambret

City

Lille

ZIP/Postal Code

59020

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xavier LIEM, Pr

Facility Name

Groupe Hospitalier Bretagne Sud

City

Lorient

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christian SIRE, Dr

Facility Name

Centre Léon Bérard

City

Lyon

Country

France

Individual Site Status

Withdrawn

Facility Name

Hopital de la Timone

City

Marseille

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sebastien SALAS, Pr

Facility Name

Hopital Nord Franche Comté - Site de Mittan

City

Montbéliard

ZIP/Postal Code

25209

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xushan SUN, Dr

Facility Name

Centre Antoine Lacassagne

City

Nice

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cyrielle SCOUARNEC, Dr

Facility Name

Institut Jean Godinot

City

Reims

ZIP/Postal Code

51726

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alain PREVOST, Dr

Facility Name

Centre Henri Becquerel

City

Rouen

ZIP/Postal Code

76038

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Florian CLATOT, Dr

Facility Name

Institut de Cancérologie Strasbourg-Europe

City

Strasbourg

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mickael BURGY, Dr

Facility Name

Institut Claudius Regaud

City

Toulouse

ZIP/Postal Code

31059

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anouchka MODESTO, Dr

Facility Name

Institut de Cancérologie de Lorraine

City

Vandoeuvre les nancy

ZIP/Postal Code

54519

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yolanda FERNADEZ DIEZ, Dr

Facility Name

Gustave Roussy

City

Villejuif

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yungan TAO, Dr

First Name & Middle Initial & Last Name & Degree

Caroline EVEN, Dr

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Learn more about this trial

Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers

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Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers (PembroMetaRT)

Squamous Cell Carcinoma of Head and Neck

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial