Radiotherapy With Pembrolizumab in Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

NCT03386357 | Terminated Phase 2 Results DMC

• 1 other identifier: IMPORTANCE, Keynote-717
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 7

Brief Summary

Randomized phase II study of immune stimulation with Pembrolizumab and radiotherapy in second line therapy of metastatic head and neck squamous cell carcinoma.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best Response According to iRECIST Criteria

  Response evaluation will be performed according to iRECIST and RECIST. These iRECIST criteria are the RECIST 1.1 criteria adapted for immunotherapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the small

  Endpoint is the best response during pembrolizumab treatment (restaging every 9 weeks up to 12 months)

Secondary Outcomes (5)

• Response Rate According to RECIST

  restaging every 9 weeks up to 12 months

• Assessment of the Duration of Response

  restaging every 9 weeks up to 12 months

• Assessment of the Progression Free Survival

  restaging every 9 weeks up to 12 months

• Assessment of the Overall Survival

  during trial treatment an follow-up, i.e. total of 24 months

• Assessment of Toxicity of the Combination of Pembrolizumab and Radiotherapy

  at every pembrolizumab administration (q3w) (up tp 12 months)

Study Arms (2)

A (pembrolizumab+RT)

EXPERIMENTAL

Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases.

Combination Product: A (pembrolizumab+RT)

B (pembrolizumab)

ACTIVE COMPARATOR

Pembrolizumab (200mg absolute, q3w) without radiotherapy

Drug: B (pembrolizumab)

Interventions

A (pembrolizumab+RT) COMBINATION_PRODUCT

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.

Also known as: Keytruda + RT

A (pembrolizumab+RT)

B (pembrolizumab) DRUG

Pembrolizumab (200mg absolute, q3w)

Also known as: Keytruda

B (pembrolizumab)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Be willing and able to provide written informed consent/assent for the trial.
• Be \>18 years of age on day of signing informed consent.
• 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).
• 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
• Histological confirmation of HNSCC
• 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)
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function
• 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.
• 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.
• 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.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• 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.
• 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.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• 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.
• 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.
• 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.
• 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.
• 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.
• History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy.
• 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.

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (7)

Bochum, St. Josef-Hospital, Abteilung für Hämatologie und Onkologie

Bochum, 44791, Germany

Location

Dresden, Onkologische Gemeinschaftspraxis

Dresden, 01307, Germany

Location

Düsseldorf, Universitätsklinikum, Klinik für Strahlentherrapie und Radiologische Onkologie

Düsseldorf, 40225, Germany

Location

Erlangen, Universitätsklinikum Strahlenklinik

Erlangen, 91054, Germany

Location

Frankfurt, Universitätsklinikum, Klinik für Strahlentherapie und Onkologie

Frankfurt, 60590, Germany

Location

Homburg, Universitätsklinikum, Klinik für Strahlentherapie und Radioonkologie

Homburg, 66421, Germany

Location

Regensburg, Universitätsklinikum, Klinik für Strahlentherapie

Regensburg, 93042, Germany

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Dr. Philipp Schubert
• Organization: Universitätsklinkum Erlangen, Strahlenklinik

studiensekretariat.ST@uk-erlangen.de

+49 9131

Study Officials

• Rainer Fietkau, Prof.

  Universitätsklinikum Erlangen, Strahlenklinik

  STUDY CHAIR

• Wilfried Budach, Prof.

  University Düsseldorf

  STUDY CHAIR

• Markus Hecht, M.D.

  Universitätsklinikum Erlangen

  PRINCIPAL INVESTIGATOR

• Hausmann Jan, M.D.

  University Düsseldorf

  STUDY CHAIR

• Udo Gaipl, Prof.

  Universitätsklinikum Erlangen

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, Controlled, randomized trial

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 29, 2017
• Study Start: July 20, 2018
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: March 27, 2026
• Results First Posted: March 12, 2026

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)