Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers
NCT ID: NCT04747054
Last Updated: 2024-10-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
102 participants
INTERVENTIONAL
2021-12-01
2029-10-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Radiotherapy added to systemic treatment
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
Pembrolizumab
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.
Loco-regional radiotherapy
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.
Chemotherapy
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
Systemic treatment
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
Pembrolizumab
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.
Chemotherapy
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
Interventions
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Pembrolizumab
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.
Loco-regional radiotherapy
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.
Chemotherapy
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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 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.
3. Eligible for treatment by pembrolizumab according to the European Marketing Authorization
4. Patient ≥18 years old
5. Performance status: 0-1 (WHO)
6. Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)
7. Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy
8. 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
9. 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
10. Patients must be affiliated to a Social Security System (or equivalent)
11. No disease progression during systemic treatment if the randomization is done after the start of pembrolizumab for the current disease
Exclusion Criteria
2. 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
3. Prior radiotherapy in the head and neck region
4. 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.
5. Known Acquired Immune Deficiency Syndrome (AIDS)
6. Known currently active infection including hepatitis B or hepatitis C
7. Patient having received live attenuated vaccine within 28 days prior to enrolment
8. Pregnant or breast feeding woman
9. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
10. Active immunodeficiency or ongoing immunosuppressive therapy
11. Active symptomatic interstitial lung disease
12. 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
13. 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
14. Prior organ transplantation including allogenic stem-cell transplantation
15. 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
16. Person deprived of their liberty or under protective custody or guardianship
17. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion
18 Years
ALL
No
Sponsors
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GORTEC
OTHER
National Cancer Institute, France
OTHER_GOV
UNICANCER
OTHER
Responsible Party
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Principal Investigators
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Yungan TAO, Dr
Role: PRINCIPAL_INVESTIGATOR
Gustave Roussy, Cancer Campus, Grand Paris
Caroline EVEN, Dr
Role: PRINCIPAL_INVESTIGATOR
Gustace Roussy
Locations
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Institut Sainte Catherine
Avignon, , France
CHU Jean Minjoz
Besançon, , France
CHU Bordeaux
Bordeaux, , France
Institut Bergonié
Bordeaux, , France
Centre François Baclesse
Caen, , France
CH Carcassonne
Carcassonne, , France
Centre Jean Perrin
Clermont-Ferrand, , France
Centre Georges François Leclerc
Dijon, , France
Centre Guillaume le Conquérant
Le Havre, , France
Centre Jean Bernard - Clinique Victor Hugo
Le Mans, , France
Centre Oscar Lambret
Lille, , France
Groupe Hospitalier Bretagne Sud
Lorient, , France
Centre Léon Bérard
Lyon, , France
Hopital de la Timone
Marseille, , France
Hopital Nord Franche Comté - Site de Mittan
Montbéliard, , France
Centre Antoine Lacassagne
Nice, , France
Institut Jean Godinot
Reims, , France
Centre Henri Becquerel
Rouen, , France
CHU de Saint Etienne
Saint-Priest-en-Jarez, , France
Institut de Cancérologie Strasbourg-Europe
Strasbourg, , France
Polyclinique de l'Ormeau
Tarbes, , France
Institut Claudius Regaud
Toulouse, , France
Hopital Privé Drome Ardeche
Valence, , France
CH Valence
Valence, , France
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, , France
Gustave Roussy
Villejuif, , France
Countries
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Central Contacts
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Other Identifiers
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2020-A02221-38
Identifier Type: OTHER
Identifier Source: secondary_id
UC-HNG-2007
Identifier Type: -
Identifier Source: org_study_id
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