Investigation of Pembrolizumab (MK-3475) as an adjunct to standard therapy before and after surgical removal of the tumor in patients with locally advanced tumor (Stage III to IVa) in the head and neck area.
Zusammenfassung der Studie
The immune system plays an important role in tumor control. Pembrolizumab is an antibody that prevents the tumor from deceiving the immune system, thereby enhancing its ability to fight it. This clinical study includes patients with newly diagnosed, locally advanced tumor in the head and neck area. The aim of the study is to investigate the efficacy of Pembrolizumab as an adjunct before and after surgery compared to the approved standard treatment. The standard therapy includes surgery and complete removal of the tumor followed by radiation with or without chemotherapy (depending on certain risk factors).
(BASEC)
Untersuchte Intervention
After careful eligibility assessment, collection of medical history, and detailed explanation, the patient is included in the study and randomly assigned to one of the two treatment arms. The probability of assignment to one of the two groups is equal (50% each). Group A receives two treatment cycles of Pembrolizumab before surgery and 15 treatment cycles of Pembrolizumab after surgery. Patients also receive radiation with or without chemotherapy (Cisplatin, three cycles) after surgery. Group B is directly operated on and will receive radiation with or without chemotherapy (Cisplatin, three cycles) after surgery. The drug therapy (Pembrolizumab, chemotherapy) is given in treatment cycles at 3-week intervals, with the medications administered intravenously via infusion on the first day of the three-week treatment cycle. After surgery, an analysis of tumor samples determines whether a patient is considered high-risk or not. High-risk patients receive a higher radiation dose and additional chemotherapy after surgery, while non-high-risk patients receive no chemotherapy and only radiation therapy. Those patients receiving Pembrolizumab or chemotherapy are treated via infusion every 3 weeks for approximately one year (Pembrolizumab) or approximately 3 months (chemotherapy). A follow-up visit is conducted 30 days after treatment ends. If the tumor has not grown, imaging via computed tomography is performed approximately every 12 weeks for 3 years, then every 6 months for another 2 years. After this time, patients are contacted approximately every 12 weeks or more frequently to assess their health status. As part of the study visits, a physical examination is conducted to document vital signs. Additionally, an electrocardiogram (ECG) is recorded, teeth and oral cavity are examined, a hearing test is performed, and neurological examinations are conducted. Blood and urine samples are also collected, and imaging studies using computed tomography, magnetic resonance imaging, or positron emission tomography (CT/MRI/PET) are performed. If disease progression is detected during imaging studies, the next steps will be discussed with the patient. A tissue sample of the tumor will also be taken and possibly tested for human papillomavirus (HPV) if the tumor is located in the back of the oral cavity or in the throat. The total study duration for each participant is approximately 5 to 6 years.
(BASEC)
Untersuchte Krankheit(en)
Approximately 600,000 people worldwide are diagnosed with a tumor in the head and neck area each year. Cancers in this body region are therefore the seventh most common. This study includes patients with newly diagnosed, locally advanced squamous cell carcinoma in the head and neck area for whom surgical removal is recommended. A total of about 600 patients worldwide will demonstrate to what extent the use of Pembrolizumab as an additional therapy to standard therapy improves treatment efficacy compared to standard therapy without Pembrolizumab.
(BASEC)
1. Newly diagnosed histologically confirmed, locally advanced, operable/non-metastatic squamous cell carcinoma in the head and neck area (Stage III to IVa). 2. A surgical intervention for tumor removal is recommended by the physician. 3. The patient has an evaluable tumor burden according to RECIST 1.1, which has been assessed by computed tomography (CT) or magnetic resonance imaging (MRI). The tumor burden assessed by computed tomography (CT) or magnetic resonance imaging (MRI) is evaluable according to RECIST 1.1. (BASEC)
Ausschlusskriterien
1. Tumors that are already more advanced and may have already metastasized. 2. Tumors outside the oropharyngeal region, larynx, lower part of the pharynx, or oral cavity, such as tumors in the nasopharynx, paranasal sinuses, or other unknown primary tumors in the head and neck area. 3. Tumors that have already been treated with radiation therapy or systemic antitumor therapy (including therapies as part of clinical trials). (BASEC)
Studienstandort
Bellinzona, Genf, Zürich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Switzerland Merck Sharp & Dohme LLC, USA
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG
(BASEC)
Allgemeine Auskünfte
Janssen-Cilag International NV
+3171 5242166
klaudia.georgi@cluttermsd.com(ICTRP)
Wissenschaftliche Auskünfte
Janssen-Cilag International NV
+3171 5242166
klaudia.georgi@cluttermsd.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
07.12.2018
(BASEC)
ICTRP Studien-ID
EUCTR2017-001139-38 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination with Standard of Care as Adjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC) (BASEC)
Wissenschaftlicher Titel
A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy for StageIII-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC) - MK-3475 (SCH 9000475) as neoadjuvant and adjuvant therapy in Stage III-IVA resectable LA HNSCC (ICTRP)
Öffentlicher Titel
MK-3475 (SCH 9000475) as neoadjuvant and adjuvant therapy in Stage III-IVA resectable LA HNSCC (Locoregionally Advanced Head and Neck Squamous Cell Carcinoma) (ICTRP)
Untersuchte Krankheit(en)
relapsing-remitting multiple sclerosis
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)
Untersuchte Intervention
Product Name: ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Product Name: ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-
Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: (ICTRP)
Studientyp
Interventional clinical trial of medicinal product (ICTRP)
Studiendesign
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: TP1 + TP2: double-blind; TP3: open-label If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1 (ICTRP)
Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes
Inclusion criteria:
1. Patients who completed study treatment at their regular Week 24 (EOT) visit within the core study (AC-058B201).
2. Signed informed consent for participating in the extension study.
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 353
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)
Exclusion criteria:
1. Patients meeting any of the study-specific criteria for permanent discontinuation of study drug, or patients receiving any of the prohibited concomitant medication.
2. Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the patient at risk by participating in the extension study.
Primäre und sekundäre Endpunkte
Main Objective: All objectives for this study are exploratory:
- To investigate the long-term safety and tolerability of ponesimod.
- To investigate the long-term efficacy of ponesimod.
- To explore the dose response relationship of 10, 20 and 40 mg
ponesimod on lymphocyte count, MRI endpoints, annualized relapse rate (ARR), and safety endpoints.;Secondary Objective: Not applicable;Primary end point(s): Only exploratory efficacy endpoints will be investigated.
The following exploratory endpoints will be analyzed:
1. Annualized confirmed relapse rate.
2. Time to first confirmed relapse
3. Time to 24-week confirmed disability progression up to end of the study.
Additional endpoints/parameters based on MRI scans, relapses as well as endpoints related to safety and tolerability will be investigated.;Timepoint(s) of evaluation of this end point: Not applicable (ICTRP)
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable (ICTRP)
Registrierungsdatum
01.11.2017 (ICTRP)
Einschluss des ersten Teilnehmers
02.02.2018 (ICTRP)
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Clinical Registry group, ClinicalTrialsEU@its.jnj.com, +3171 5242166, Janssen-Cilag International NV (ICTRP)
Sekundäre IDs
AC-058B202, 2009-011470-15-FI (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011470-15 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
Multicenter, randomized, double-blind, parallel-group extension to study AC 058B201 to investigate the long-term safety, tolerability, and efficacy of 10, 20, and 40 mg/day ponesimod, an oral S1P1 receptor agonist, in patients with relapsing-remitting multiple sclerosis (ICTRP)
Link zu den Ergebnissen im Primärregister
nicht verfügbar