PEmbrolizumab Combined With Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

NCT02819752 | Terminated Phase 1 Results DMC

• 1 other identifier: CCR4325
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to establish whether the combination of pembrolizumab (MK-3475) and conventional cisplatin-based chemoradiotherapy is tolerable and results in acceptable levels of acute and late toxicity in patients with stage IV LA-SCCHN. In particular, the study will provide data on the levels of mucosal and cutaneous toxicity within the radiation fields, as these are the primary acute toxicities associated with this treatment regimen. In addition, toxicity outside the radiation portals (which may theoretically be exacerbated by radiation) will be studied. However, all toxicity will be monitored. This study will also give an indication of the activity of pembrolizumab in LA-SCCHN because we are deliberately selecting a group of patients with high- and intermediate-risk disease who have a significant chance of experiencing loco-regional or systemic failure.

Conditions

Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma

Keywords

squamous cell carcinoma; squamous cell carcinoma of the head and neck

Outcome Measures

Primary Outcomes (2)

• Number and Percentage of Patients With Dose Limiting Toxicities (DLT).

  To establish the maximum tolerated dose that can safely be combined with platin-based chemoradiotherapy in patients with HPV-ve and HPV+ve LA-SCCHN.

  Six weeks after the completion of chemoradiotherapy

• Acute Toxicity as Measured During Treatment by CTCAE v4.0

  Count and percentage of patients with any CTCAE graded toxicity from start of trial treatment until 6 weeks following end of treatment

  Up until 6 weeks after the end of chemoradiotherapy (week 14 of the study)

Secondary Outcomes (4)

• Percentage of Progression Free Survival at 6, 12 and 24 Months Post Treatment Start.

  Six months, one year and two years

• Percentage of Overall Survival at 6, 12 and 24 Months

  Six months, one year and two years

• Percentage of Patients With Clinical Benefit (CR/PR/SD) Using RECIST at 6, 12 and 24 Months

  Six months, one year and two years

• Percentage of Patients With Any Grade 1 Plus RTOG Toxicities

  52 weeks from the end of radiation therapy (week 7)

Other Outcomes (3)

• Identify Biomarkers and Correlate With Clinical Benefit, as Defined by RECIST v1.1

  through study completion (24 months)

• Analysis of Circulating Free Tumour DNA

  Screening, week 3, week 9 and week 15

• Immunohistochemical Analysis to Identify Immune Infiltrates

  through study completion (24 months)

Study Arms (2)

HPV-ve stage IVA/IVB SCCHN

EXPERIMENTAL

Pembrolizumab and Chemoradiotherapy

Drug: Pembrolizumab; Radiation: Radiotherapy; Drug: Chemotherapy

HPV+ve stage IVA/IVB SCCHN

EXPERIMENTAL

Pembrolizumab and Chemoradiotherapy

Drug: Pembrolizumab; Radiation: Radiotherapy; Drug: Chemotherapy

Interventions

Pembrolizumab DRUG

Pembrolizumab

Also known as: MK-3475/pembrolizumab (KEYTRUDA®)

HPV+ve stage IVA/IVB SCCHN; HPV-ve stage IVA/IVB SCCHN

Radiotherapy RADIATION

Radiotherapy - Standard Treatment

Also known as: 70 Gy in 35 fractions

HPV+ve stage IVA/IVB SCCHN; HPV-ve stage IVA/IVB SCCHN

Chemotherapy DRUG

Chemotherapy - Standard Treatment

Also known as: Cisplatin 100 mg/m2 or Carboplatin Area under the curve (AUC) = 5) on days 1, 22, 43

HPV+ve stage IVA/IVB SCCHN; HPV-ve stage IVA/IVB SCCHN

Eligibility Criteria

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

You may qualify if:

• Have treatment naive and histologically confirmed high-/intermediate-risk LA-SCCHN
• Be willing and able to provide written informed consent for the trial.
• Be \> or = 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumour lesion.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Be fit for definitive platin-based chemoradiation therapy.
• Demonstrate adequate organ function as defined in table 1, all screening labs should be performed within 10 days of confirmation of study eligibility.
• Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patient s of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 6.7.2). Patient s of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male patient s should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has received prior radiotherapy to the head and neck region.
• 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 had a prior monoclonal antibody, chemotherapy, targeted small molecule therapy, or radiation therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient s 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.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patient s with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patient s with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has active tuberculosis.
• Has known hypersensitivity to pembrolizumab or any of its excipients.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• 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.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Institute of Cancer Research, United Kingdom: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Royal Marsden Hospital NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

pembrolizumab; Radiotherapy; Drug Therapy; Cisplatin; Area Under Curve

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Statistics as Topic; Epidemiologic Methods; Investigative Techniques; Pharmacokinetics; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena; Public Health; Environment and Public Health

Results Point of Contact

• Title: PEACH Senior Trial Manager
• Organization: The Royal Marsden NHS Foundation Trust

peach.trial@rmh.nhs.uk

(+44) 02089156666

Study Officials

• Prof Kevin Harrington, CTU

  Consultant Clinical Oncologist

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel studies in HPV-ve and HPV +ve disease will be conducted (note these patients may have different patterns of co-morbidity and, hence, different treatment-related toxicities). Both the HPV-ve and HPV+ve arms will run simultaneously.

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: June 30, 2016
• Study Start: July 12, 2017
• Primary Completion: November 28, 2019
• Study Completion: November 28, 2019
• Last Updated: April 9, 2026
• Results First Posted: December 18, 2025

Record last verified: 2026-03

Locations

GB (1)