JOURNAL ONKOLOGIE – STUDIE

Radiotherapy With Pembrolizumab in Metastatic HNSCC

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT03386357

Studienbeginn:
Juli 2018

Letztes Update:
14.08.2023

Wirkstoff:
B (pembrolizumab)

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
University of Erlangen-Nürnberg Medical School

Collaborator:
-

Studienleiter

Rainer Fietkau, Prof.
Study Chair
Universitätsklinikum Erlangen, Strahlenklinik

Wilfried Budach, Prof.
Study Chair
Universitätsklinikum Düsseldorf

Markus Hecht, M.D.
Principal Investigator
Universitätsklinikum Erlangen

Hausmann Jan, M.D.
Study Chair
Universitätsklinikum Düsseldorf

Udo Gaipl, Prof.
Study Chair
Universitätsklinikum Erlangen

Kontakt

Annett Kallies, Ph.D.
Kontakt:
Phone: ++49(0)9131-85-33968
E-Mail: st-studiensekretariat@uk-erlangen.de» Kontaktdaten anzeigen

Markus Hecht, M.D.
Kontakt:
Phone: ++49(0)9131-85-33968
E-Mail: markus.hecht@uk-erlangen.de» Kontaktdaten anzeigen

Studienlocations
(3 von 7)

Bochum, St. Josef-Hospital, Abteilung für Hämatologie und Onkologie
44791 Bochum
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Anke Reinacher-Schick, Prof.
Phone: +49234-509-3591
E-Mail: anke.reinacher@rub.de

Linda Wingender, MD
E-Mail: l.brand@klinikum-bochum.de» Ansprechpartner anzeigen

Dresden, Onkologische Gemeinschaftspraxis
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thomas Illmer, M.D.
Phone: +49351/4472340
E-Mail: illmer@onkologie-dresden.net

Jörgen Radke, MD» Ansprechpartner anzeigen

Düsseldorf, Universitätsklinikum, Klinik für Strahlentherrapie und Radiologische Onkologie
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Bálint Tamaskovics, M.D.
Phone: +49221/81 16894
E-Mail: balint.tamaskovics@med.uni-duesseldorf.de

Jan Haussmann, MD
E-Mail: jan.haussmann@med.uni-duesseldorf.de» Ansprechpartner anzeigen

Erlangen, Universitätsklinikum Strahlenklinik
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Markus Hecht, MD
E-Mail: markus.hecht@uk-erlangen.de

Rainer Fietkau, Prof.
E-Mail: rainer.fietkau@uk-erlangen.de» Ansprechpartner anzeigen

Frankfurt, Universitätsklinikum, Klinik für Strahlentherapie und Onkologie
60590 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Claus Rödel, M.D.
E-Mail: claus.rödel@kgu.de

Jens Müller von der Grün
E-Mail: jens.Muellervondergruen@kgu.de» Ansprechpartner anzeigen

Homburg, Universitätsklinikum, Klinik für Strahlentherapie und Radioonkologie
66421 Homburg
(Saarland)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Patrick Melchior, M.D.
Phone: +496841/162-4820
E-Mail: patrick.melchior@uks.eu

Marcus Niewald, MD
E-Mail: marcus.niewald@uks.eu» Ansprechpartner anzeigen

Regensburg, Universitätsklinikum, Klinik für Strahlentherapie
93042 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Oliver Kölbl, Prof.
E-Mail: oliver.koelbl@ukr.de

Daniel Heudobler, MD
E-Mail: daniel.heudobler@ukr.de» Ansprechpartner anzeigen

Alle anzeigen

Studien-Informationen

Detailed Description:

This is an open-label, randomized, prospective, multicenter phase II clinical trial of

pembrolizumab with or without local radiotherapy in patients with recurrent and/or metastatic

HNSCC after progression to platinum-based therapy.

All patients will receive pembrolizumab 200mg absolute dose administered every third week.

Patients in treatment arm A will receive radiotherapy of one, two or three metastases with a

total tumor volume of at least 10cm³ intended to induce tumor cell death acting as an in situ

vaccination. Radiotherapy will be performed conventionally fractioned with single doses of

3Gy to a total dose of 36Gy. There will be a strict time schedule. Radiotherapy will always

start on Wednesday. After application of the third radiation dose (Friday) the patients will

receive pembrolizumab. After an interruption of radiotherapy for two days (Saturday, Sunday),

radiotherapy will be continued. Pembrolizumab will be continued on an every three week

schedule until confirmed disease progression according to iRECIST criteria, unacceptable

toxicity, patient's wish to stop therapy or a maximal treatment time of 12 months.

Tumor assessment will be performed every 9 weeks and will be evaluated according to iRECIST

and RECIST. For each patient the same assessment method will be used throughout the study.

Toxicity will be assessed according to CTCAE 4.0.

Ein-/Ausschlusskriterien

Inclusion Criteria:

In order to be eligible for participation in this trial, the subject must:

1. Be willing and able to provide written informed consent/assent for the trial.

2. Be >18 years of age on day of signing informed consent.

3. Metastatic HNSCC (at least two distinct lesions: Lesion planned for radiotherapy with

≥10 ml tumor volume, or ≥3 lesions: 1 lesion planned for radiotherapy with ≥10 ml

tumor volume or 2 lesions planned for radiotherapy with a cumulative tumor volume

≥10ml) OR Locally recurrent HNSCC not suitable for curative local treatment within or

outside the previously irradiated tissue (at least two distinct lesions: Lesion

planned for radiotherapy with ≥10 ml tumor volume, or ≥3 lesions: 1 lesion planned for

radiotherapy with ≥10 ml tumor volume or 2 lesions planned for radiotherapy with a

cumulative tumor volume ≥10ml).

4. Progression to first line platinum-based or any second/third line chemotherapy OR

Progression within 6 months after platinum-based radiochemotherapy of locally advanced

disease

5. Histological confirmation of HNSCC

6. Have at least one measurable lesion according to iRECIST that receives less than 10%

of the prescribed dose of the irradiated lesion(s) (not considering doses from

previous radiotherapy)

7. Have a performance status of 0-1 on the ECOG Performance Scale.

8. Demonstrate adequate organ function

9. Female subject of childbearing potential should have a negative urine or serum

pregnancy within 72 hours prior to receiving the first dose of study medication. If

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

will be required.

10. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an

adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the

course of the study through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred

contraception for the subject.

11. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate

method of contraception as outlined in Section 5.7.1- Contraception, starting with the

first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception

for the subject.

-

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

1. Is currently participating and receiving study therapy or has participated in a study

of an investigational agent and received study therapy or used an investigational

device within 4 weeks of the first dose of treatment.

2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any

other form of immunosuppressive therapy within 7 days prior to the first dose of trial

treatment.

3. Has a known history of active TB (Bacillus Tuberculosis)

4. Hypersensitivity to pembrolizumab or any of its excipients.

5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study

day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events

due to agents administered more than 4 weeks earlier.

6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy

within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at

baseline) from adverse events due to a previously administered agent.

- Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and

may qualify for the study.

- Note: If subject received major surgery, they must have recovered adequately from

the toxicity and/or complications from the intervention prior to starting

therapy.

7. Has a known additional malignancy that is progressing or requires active treatment.

Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the

skin that has undergone potentially curative therapy or in situ cervical cancer.

8. Has known active central nervous system (CNS) metastases and/or carcinomatous

meningitis. Subjects with previously treated brain metastases may participate provided

they are stable (without evidence of progression by imaging for at least four weeks

prior to the first dose of trial treatment and any neurologic symptoms have returned

to baseline), have no evidence of new or enlarging brain metastases, and are not using

steroids for at least 7 days prior to trial treatment. This exception does not include

carcinomatous meningitis which is excluded regardless of clinical stability.

9. Has 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.

10. History of (non-infectious) pneumonitis that required steroids, evidence of

interstitial lung disease or active, non-infectious pneumonitis

11. Has an active infection requiring systemic therapy.

12. Has a history or current evidence of any condition, therapy, or laboratory abnormality

that might confound the results of the trial, interfere with the subject's

participation for the full duration of the trial, or is not in the best interest of

the subject to participate, in the opinion of the treating investigator.

13. Has known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the trial.

14. Is pregnant or breastfeeding, or expecting to conceive or father children within the

projected duration of the trial, starting with the pre-screening or screening visit

through 120 days after the last dose of trial treatment.

15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

16. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

17. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA

[qualitative] is detected).

18. Has received a live vaccine within 30 days of planned start of study therapy. Note:

Seasonal influenza vaccines for injection are generally inactivated flu vaccines and

are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live

attenuated vaccines, and are not allowed.

19. Have a performance status of ≥2 on the ECOG Performance Scale.

Studien-Rationale

Primary outcome:

1. Best response according to iRECIST criteria (Time Frame - Endpoint is the best response during pembrolizumab treatment (restaging every 9 weeks up to 12 months)):
Local radiotherapy will significantly improve the overall response rate according to iRECIST

Secondary outcome:

1. Response rate according to RECIST (Time Frame - restaging every 9 weeks up to 12 months):
RECIST 1.1 criteria

2. Assessment of target lesion (Time Frame - restaging every 9 weeks up to 12 months):
changes of the size of a (not irradiated) target lesion will be measured (%)

3. Assessment of the duration of response (Time Frame - restaging every 9 weeks up to 12 months):
The duration of the response will be evaluated in responding patients.

4. Assessment of the progression free survival (Time Frame - restaging every 9 weeks up to 12 months):
progression free survival (in months)

5. Assessment of the overall survival (Time Frame - restaging every 9 weeks up to 12 months):
Overall survival (in months)

6. Assessment of toxicity of the combination of pembrolizumab and radiotherapy (Time Frame - at every pembrolizumab administration (q3w) (up tp 12 months)):
Toxicity will be evaluated according to CTCAE 4.0

Studien-Arme

Experimental: A (pembrolizumab+RT)
Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases.
Active Comparator: B (pembrolizumab)
Pembrolizumab (200mg absolute, q3w) without radiotherapy

Geprüfte Regime

A (pembrolizumab+RT) (Keytruda + RT):
Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.
B (pembrolizumab) (Keytruda):
Pembrolizumab (200mg absolute, q3w)

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"Radiotherapy With Pembrolizumab in Metastatic HNSCC"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!