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

NCT04747054 | Recruiting Phase 3

• 2 other identifiers: UC-HNG-20072020-A02221-38
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 26

Brief Summary

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

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (9)

• Overall survival (OS)

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

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

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

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

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

• Objective response rate (ORR)

  At 18 weeks and 27 weeks

• Loco-regional progression

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

Study Arms (2)

Radiotherapy added to systemic treatment

EXPERIMENTAL

Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity. Loco-regional radiotherapy(RT) depending on the RT timing : * Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. If the investigator decides before randomization to add chemotherapy and depending on the RT timing: * Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab. * RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles

Drug: Pembrolizumab; Radiation: Loco-regional radiotherapy; Drug: Chemotherapy

Systemic treatment

ACTIVE COMPARATOR

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 area under the curve (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

Drug: Pembrolizumab; Drug: Chemotherapy

Interventions

Pembrolizumab DRUG

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.

Also known as: KEYTRUDA

Radiotherapy added to systemic treatment; Systemic treatment

Loco-regional radiotherapy RADIATION

Depending on the choice of radiotherapy timing: * Before 3 cycles of pembrolizumab with or without chemotherapy : radiotherapy could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab with or without chemotherapy : radiotherapy could start at any time after 3rd cycle (C3D1) and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. Dose/fraction of radiotherapy: 54 Gy/18 fractions (recommended schedule) or 70Gy/33-35 fractions or other curative dose/fraction schedules with shorter duration and biologically equivalent dose of at least 60Gy at the discretion of local investigators, 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. Other cycles of pembrolizumab will be administered during and after radiotherapy.

Radiotherapy added to systemic treatment

Chemotherapy DRUG

If the investigator decide to add chemotherapy with pembrolizumab, and depending on the radiotherapy timing: * Start of radiotherapy planned before 3rd cycle: Chemotherapy could be delayed after the end of radiotherapy and start from cycle 3 or 4 of pembrolizumab. Administration of chemotherapy can be delayed in case of non resolved grade 3 or higher toxicity from radiotherapy. * Radiotherapy planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will combine carboplatin AUC 5mg/mL/min or cisplatin 100mg/m² every 3 weeks with 5-FU 1000mg/m²/j during 4 days every 3 weeks for a maximum of 6 cycles

Radiotherapy added to systemic treatment; Systemic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with 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:
• a. If randomization is done before treatment start: i. Absolute neutrophil count ≥1.5 × 10⁹/L ii. Platelet ≥100 × 10⁹/L iii. Hemoglobin ≥90 g/L iv. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) v. Bilirubin ≤1.5 × ULN. vi. Serum albumin ≥25 g/L vii. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) viii. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L. b. If randomization if done after treatment start i. Absolute neutrophil count ≥1.0 × 10⁹/L ii. Platelet ≥75 × 10⁹/L iii. Hemoglobin ≥85 g/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)
• No disease progression during systemic treatment if the randomization is done after the start of pembrolizumab for the current disease

You may not qualify if:

• Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
• Prior radiotherapy in the head and neck region
• Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +/- chemotherapy for the current cancer for a maximum of 6 cycles). 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. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.
• 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

Sponsors & Collaborators

• UNICANCER: lead
• GORTEC: collaborator
• National Cancer Institute, France: collaborator

Study Sites (26)

Institut Sainte Catherine

Avignon, 84000, France

RECRUITING

CHU Jean Minjoz

Besançon, 25030, France

RECRUITING

CHU Bordeaux

Bordeaux, 33075, France

RECRUITING

Institut Bergonié

Bordeaux, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

RECRUITING

CH Carcassonne

Carcassonne, 1A810, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Guillaume le Conquérant

Le Havre, France

SUSPENDED

Centre Jean Bernard - Clinique Victor Hugo

Le Mans, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Groupe Hospitalier Bretagne Sud

Lorient, France

RECRUITING

Centre Léon Bérard

Lyon, France

WITHDRAWN

Hopital de la Timone

Marseille, France

RECRUITING

Hopital Nord Franche Comté - Site de Mittan

Montbéliard, 25209, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Institut Jean Godinot

Reims, 51726, France

RECRUITING

Centre Henri Becquerel

Rouen, 76038, France

RECRUITING

CHU de Saint Etienne

Saint-Priest-en-Jarez, 42270, France

NOT YET RECRUITING

Institut de Cancérologie Strasbourg-Europe

Strasbourg, France

RECRUITING

Polyclinique de l'Ormeau

Tarbes, 65000, France

NOT YET RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Hopital Privé Drome Ardeche

Valence, 26000, France

NOT YET RECRUITING

CH Valence

Valence, 26953, France

NOT YET RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Carcinoma, Squamous Cell; Carcinoma

Interventions

pembrolizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Yungan TAO, Dr

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

• Caroline EVEN, Dr

  Gustace Roussy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NICOLAS DE SOUSA CARVALHO

CONTACT

0171936709; n-de-sousa@unicancer.fr

LAURE MONARD

CONTACT

01 73 79 73 09; l-monard@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 10, 2021
• Study Start: December 1, 2021
• Primary Completion: October 1, 2025
• Study Completion (Estimated): October 1, 2029
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (26)