JOURNAL ONKOLOGIE – STUDIE

Pembrolizumab and Lenvatinib After Definitive Chemoradiation of Locally Advanced HNSCC

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05433116

Studienbeginn:
Mai 2023

Letztes Update:
15.09.2023

Wirkstoff:
Pembrolizumab, Lenvatinib

Indikation (Clinical Trials):
Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Universität des Saarlandes

Collaborator:
-

Studienleiter

Markus Hecht, Prof.
Principal Investigator
Saarland University Medical Center, Clinic for Radiotherapy and Radiooncology

Antoniu-Oreste Gostian, MD
Study Chair
University Hospital Straubing, Clinic for Otolaryngology, Head and Neck and Facial Plastic Surgery

Henning Kahl, MD
Study Chair
University Hospital Augsburg, Radiation Oncology

Rainer Fietkau, Prof.
Study Chair
University Hospital Erlangen, Radiation Oncology

Udo Gaipl, Prof.
Study Chair
University Hospital Erlangen, Radiation Oncology

Markus Eckstein, MD
Study Chair
University Hospital Erlangen, Pathology

Kontakt

Wiebke Pirschel, M. Sc.
Kontakt:
Phone: +49684116
Phone (ext.): 24606
E-Mail: wiebke.pirschel@uks.eu» Kontaktdaten anzeigen

Markus Hecht, Prof.
Kontakt:
Phone: +49684116
Phone (ext.): 24606
E-Mail: markus.hecht.clinicaltrials@uks.eu» Kontaktdaten anzeigen

Studienlocations
(3 von 9)

University Hospital Ulm, Otolaryngology & Head and Neck Surgery
89070 Ulm
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps

University Hospital Regensburg, Clinic and Polyclinic for Radiotherapy
93053 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps

University Hospital Augsburg, Radiation Oncology
86156 Augsburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps

University Hospital Erlangen, Radiation Oncology
91054 Erlangen
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps

University Hospital Frankfurt/M, Center for Radiology
60590 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps

University Hospital Düsseldorf, Radiation Oncology
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps

Saarland University Medical Center and Saarland University Faculty of Medicine, Clinic for Radiotherapy and Radiooncology
66421 Homburg
(Saarland)
GermanyRekrutierend» Google-Maps

Hospital Chemnitz, Radiation Oncology
09116 Chemnitz
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps

Gemeinschaftspraxis Hämatologie-Onkologie
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This is an open-label, single-arm, prospective multicenter phase II clinical trial to

determine the efficacy and safety combined pembrolizumab and lenvatinib as maintenance

therapy after definitive radiochemotherapy of locally advanced head and neck squamous cell

carcinoma (HNSCC). The trial will be conducted in conformance with Good Clinical Practices

and subjects will be enrolled into the trial by signing the informed consent form (ICF). Only

subjects with PD-L1 positive (CPS≥1) tumors according to centralized reference pathologic

assessment can be enrolled. Subjects without disease progression in the study screening CT

(compared to radiochemotherapy baseline CT) that fulfil all further eligibility criteria can

enter the trial after completion of definitive radiochemotherapy. Sites will be required to

submit tissue samples for translational research to central pathology.

After confirmed study inclusion, patients will receive combined pembrolizumab and lenvatinib

treatment. Pembrolizumab will be administered intravenously at a dose of 200mg q3w and

lenvatinib at a dose of 20mg once daily orally. The first dose of pembrolizumab has to be

administered within 14 days after completion of radiochemotherapy. Treatment with lenvatinib

will start concomitant to cycle 2 of pembrolizumab. Treatment will be continued until disease

progression, unacceptable adverse event(s) or until the subject has received 12 months of

treatment (i.e. 17 doses of pembrolizumab). Afterwards patients will enter follow-up until

24months since study inclusion.

It is planned to enroll 47 patients. Primary endpoint of the trial is the event-free survival

(EFS) rate at 2 years. The aim of the trial is to achieve a 2-year EFS rate of 70% (compared

to 55% in the historic controls). This improvement is considered to be a clinically relevant

advantage.

Ein-/Ausschlusskriterien

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria

apply:

1. Male/female participants who are at least 18 years of age on the day of signing

informed consent

2. Pathologically proven new diagnosis of squamous cell carcinoma (HNSCC) of the oral

cavity, oropharynx, hypopharynx or supraglottic larynx stage III-IVB according to TMM

8th edition

3. PD-L1 combined positive score (CPS) ≥1 (in sample prior to radiochemotherapy) by

central pathology review

4. Completed definitive radiochemotherapy up to at least 68Gy with at least 200mg/m² body

surface area concomitant Cisplatin.

5. No progression during radiochemotherapy. Study screening CT has to be compared to

radiochemotherapy baseline CT. (Study screening CT may be performed before the end of

radiochemotherapy, whereas a minimum radiation dose of 50Gy has to be administered at

the time point of the study screening CT.)

6. Male participants:

A male participant must agree to use a contraception as detailed in Appendix 3 of this

protocol during the treatment period and for at least 120 days after the last dose of

study treatment (pembrolizumab or lenvatinib, whichever is administered last) and

refrain from donating sperm during this period. In addition, contraception has to be

used for 180 days after the last dose of cisplatin.

7. Female participants:

A female participant is eligible to participate if she is not pregnant, not

breastfeeding, and at least one of the following conditions applies: a. Not a woman of

childbearing potential (WOCBP) OR b. A WOCBP who agrees to follow the contraceptive

guidance during the treatment period and for at least 120 days after the last dose of

study treatment (pembrolizumab or lenvatinib, whichever is administered last). In

addition, contraception has to be used for 180 days after the last dose of cisplatin.

8. The participant provides written informed consent for the trial.

9. Have measurable disease based on RECIST 1.1.

10. Have provided archival tumor tissue sample with sufficient tumor content.

Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.

11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Evaluation of ECOG is to be performed within 7 days prior to the first dose of study

intervention.

12. Have adequate organ function. Specimens must be collected within 10 days prior to the

start of study intervention.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Have tumor infiltration/perforation of the skin or cervical fistula (either at

timepoint of study inclusion or prior to radiochemotherapy)

2. Have radiographic evidence of major blood vessel invasion/infiltration or tumor

demonstrates >90-degree abutment or encasement of a major blood vessel.

3. Had prior radical surgery for the head and neck cancer under study or induction

chemotherapy with more than one cycle prior to definitive radiochemotherapy. Patients

with single cycle induction chemotherapy prior radiochemotherapy can be included.

4. WOCBP who have a positive urine or serum pregnancy test within 72 hours prior to. If

the urine test is positive or cannot be confirmed as negative, a serum pregnancy test

will be required.

5. Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with

an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,

OX-40, CD137).

6. Have received prior systemic anti-cancer therapy including investigational agents

within 4 weeks prior to study drug administration (except from cisplatin concomitant

to radiochemotherapy).

7. Have received a live vaccine or live-attenuated vaccine within 30 days prior to the

first dose of study drug. Administration of killed vaccines is allowed.

8. Are currently participating in or have participated in a study of an investigational

agent or have used an investigational device within 4 weeks prior to the first dose of

study intervention.

9. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior to the first dose of study drug.

10. Have a known additional malignancy that is progressing or have required active

treatment within the past 3 years. Participants with basal cell carcinoma of the skin,

squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma,

cervical cancer in situ) that have undergone potentially curative therapy are not

excluded.

11. Have distant metastases.

12. Have severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of

their excipients.

13. Have active autoimmune disease that has required systemic treatment in the past 2

years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive

drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid

replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a

form of systemic treatment and is allowed.

14. Have a history of (non-infectious) pneumonitis/interstitial lung disease that required

steroids or has current pneumonitis/interstitial lung disease.

15. Have an active infection requiring systemic therapy.

16. Have a known history of Human Immunodeficiency Virus (HIV) infection.

17. Have a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]

reactive) or known active Hepatitis C virus (defined as HCV RNA is detected)

infection.

18. Have a history or current evidence of any condition, therapy, or laboratory

abnormality that might confound the results of the study, interfere with the

participant's participation for the full duration of the study, or is not in the best

interest of the participant to participate, in the opinion of the treating

investigator.

19. Have known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the trial.

20. Are pregnant or breastfeeding or expecting to conceive or father children within the

projected duration of the study, starting with the screening visit through 120 days

after the last dose of trial treatment. (as documented by a positive beta-human

chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a

minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]).

21. Have had an allogenic tissue/solid organ transplant.

22. Have uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) in

spite of an optimized regimen of antihypertensive medication.

23. Have clinically relevant electrolyte abnormalities that have not been corrected.

24. Have significant cardiovascular impairment: history of congestive heart failure

greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial

infarction or stroke within 6 months of the first dose of study drug, or cardiac

arrhythmia requiring medical treatment at Screening.

25. Have/had bleeding or thrombotic disorders or subjects at risk for severe hemorrhage.

The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery)

should be considered because of the potential risk of severe hemorrhage associated

with tumor shrinkage/necrosis following lenvatinib therapy.

26. Have > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for

quantitative assessment indicates that the urine protein is <1 g/24 hours.

Studien-Rationale

Primary outcome:

1. Event-free survival (EFS) rate (Time Frame - 2 years):
To study efficacy of pembrolizumab/lenvatinib maintenance therapy after definitive radiochemotherapy of locally advanced HNSCC to prolong the event-free survival (EFS) rate at 2 years

Secondary outcome:

1. Event-free survival (EFS) (continuous) (Time Frame - 2 years):
Pembrolizumab/lenvatinib maintenance therapy will improve further efficacy endpoints compared to historic control

2. Locoregional control (Time Frame - Restaging 12-13 weeks after completion of radiotherapy; Follow-up every 24 weeks):
Locoregional progression will be evaluated by RECIST 1.1 criteria

3. Toxicity of Pembrolizumab/lenvatinib (Time Frame - until safety follow-up (1 year treatment + 30 days)):
Toxicity will be evaluated according to CTCAE v5.0 criteria

Geprüfte Regime

Pembrolizumab (Keytruda):
i.v., 200mg absolute, q3w, starting within 14 days after completion of radiochemotherapy
Lenvatinib (Lenvima):
20mg once daily orally, start concomitant to cycle 2 of pembrolizumab

Quelle: ClinicalTrials.gov

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