Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study on the Efficacy of Radiotherapy Added to Pembrolizumab in Newly Diagnosed Metastatic Head and Neck Cancers (PembroMetaRT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04747054
Recruitment Status : Recruiting
First Posted : February 10, 2021
Last Update Posted : December 3, 2021
Sponsor:
Collaborators:
GORTEC
National Cancer Institute, France
Information provided by (Responsible Party):
UNICANCER

Tracking Information
First Submitted Date  ICMJE February 5, 2021
First Posted Date  ICMJE February 10, 2021
Last Update Posted Date December 3, 2021
Actual Study Start Date  ICMJE December 1, 2021
Estimated Primary Completion Date October 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2021)
Progression free-survival rate at 1 year [ Time Frame: From randomization to disease progression or death, up to 1 year. ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2021)
  • Overall survival (OS) [ Time Frame: From randomization to death from any cause, up to 5 years. ]
    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.
  • Progression-free survival (PFS) [ Time Frame: From randomization to disease progression or death, up to 3 years. ]
    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.
  • Quality of life questionnaire - Core 30 (QLQ-C30) [ Time Frame: At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years ]
    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) [ Time Frame: At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years ]
    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) [ Time Frame: At 18 weeks ]
    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 [ Time Frame: From randomization to loco-regional progression, up to 5 years. ]
    Locoregional disease progression is defined as the time from randomization to the first documented locoregional progression evaluated by RECIST v1.1.
  • Distant progression [ Time Frame: From randomization to distant progression, up to 5 years. ]
    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) [ Time Frame: Up to 5 years after randomization. ]
    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 [ Time Frame: Throughout study completion, up to 5 years. ]
    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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on the Efficacy of Radiotherapy Added to Pembrolizumab in Newly Diagnosed Metastatic Head and Neck Cancers
Official Title  ICMJE Randomized Trial of Loco-regional Radiotherapy Added to Pembrolizumab Versus Pembrolizumab Alone for Patients With Newly Diagnosed Head and Neck Squamous Cell Carcinoma With Synchronous Metastases
Brief Summary Trial evaluating the efficacy of radiotherapy added to pembrolizumab compared to pembrolizumab alone for patients with newly diagnosed head and neck carcinoma with metastases
Detailed Description Comparative interventional prospective phase 3, randomised, open-label, multicentric trial comparing the combination of radiotherapy and pembrolizumab to pembrolizumab alone as first line treatment of patients with newly diagnosed head and neck squamous cell carcinoma with synchronous metastases.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Squamous Cell Carcinoma of Head and Neck
Intervention  ICMJE
  • Drug: 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.
    Other Name: KEYTRUDA
  • Radiation: Loco-regional radiotherapy
    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.
Study Arms  ICMJE
  • Experimental: Radiotherapy added to pembrolizumab

    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.

    Interventions:
    • Drug: Pembrolizumab
    • Radiation: Loco-regional radiotherapy
  • Active Comparator: pembrolizumab alone
    Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity.
    Intervention: Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2021)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2029
Estimated Primary Completion Date October 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.
  2. 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)
  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 one month prior to initiation of study treatment:

    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.
  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)

Exclusion Criteria:

  1. Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
  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 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
  5. Uncontrolled head and neck loco-regional grade ≥3 (by CTCAE v5.0) symptoms including bleeding, pain, dysphagia (feeding tube permitted), or dyspnea (tracheotomy permitted)
  6. Known Acquired Immune Deficiency Syndrome (AIDS)
  7. Known currently active infection including hepatitis B or hepatitis C
  8. Patient having received live attenuated vaccine within 28 days prior to enrolment
  9. Pregnant or breast feeding woman
  10. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
  11. Active immunodeficiency or ongoing immunosuppressive therapy
  12. Active symptomatic interstitial lung disease
  13. 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
  14. 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
  15. Prior organ transplantation including allogenic stem-cell transplantation
  16. 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
  17. Person deprived of their liberty or under protective custody or guardianship
  18. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: NICOLAS DE SOUSA CARVALHO 0171936709 n-de-sousa@unicancer.fr
Contact: LAURE MONARD 01 73 79 73 09 l-monard@unicancer.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04747054
Other Study ID Numbers  ICMJE UC-HNG-2007
2020-A02221-38 ( Other Identifier: ANSM )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Responsible Party UNICANCER
Study Sponsor  ICMJE UNICANCER
Collaborators  ICMJE
  • GORTEC
  • National Cancer Institute, France
Investigators  ICMJE
Principal Investigator: Yungan TAO Gustave Roussy, Cancer Campus, Grand Paris
PRS Account UNICANCER
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP