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

Sponsor
Royal Marsden NHS Foundation Trust (Other)
Overall Status
Terminated
CT.gov ID
NCT02819752
Collaborator
Institute of Cancer Research, United Kingdom (Other), Merck Sharp & Dohme LLC (Industry)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This will be a single centre phase 1 dose-escalation study to confirm the safety of combining pembrolizumab with standard platin-based chemoradiotherapy in patients with stage IV high- and intermediate-risk locally-advanced squamous cell carcinoma of the head and neck (LA-SCCHN). 6-36 patients (18 HPV+ve and 18 HPV-ve) will be recruited in a standard 3+3 dose-escalation trial design with an expansion cohort at the maximum tolerated dose (or 200 mg, if no DLT is defined). A pre-loading dose of 100 or 200mg (dependent on dosing level) of pembrolizumab will be given once the patient has completed the screening period. Patients will then return 2 weeks later to begin cycle 1 of a regimen of pembrolizumab 3 weekly at a dose of 100 or 200mg (dependent on dosing level) for a total of 7 cycles (3 during chemoradiotherapy and 4 after chemoradiotherapy).

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). The primary endpoint of the study will be safety and tolerability. Dose-limiting acute toxicity will be assessed during administration of study drug according to CTCAEv4.0. The maximum tolerated dose of study drug (or 200 mg in the absence of DLT) will be used in a subsequent randomised phase 2 study comparing standard-of-care therapy with standard-of-care therapy plus study drug.

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase I Dose-escalation Study of PEmbrolizumab (MK3475) Anti-PD1 Immune Checkpoint Inhibitor Combined With Radical Chemoradiotherapy in Patients With Stage IV Squamous Cell Carcinoma of the Head and Neck
Actual Study Start Date :
Jul 12, 2017
Actual Primary Completion Date :
Nov 28, 2019
Actual Study Completion Date :
Nov 28, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: HPV-ve stage IVA/IVB SCCHN

Pembrolizumab and Chemoradiotherapy

Drug: Pembrolizumab
Pembrolizumab
Other Names:
  • MK-3475/pembrolizumab (KEYTRUDA®)
  • Radiation: Radiotherapy
    Radiotherapy - Standard Treatment

    Drug: Chemotherapy
    Chemotherapy - Standard Treatment

    Experimental: HPV+ve stage IVA/IVB SCCHN

    Pembrolizumab and Chemoradiotherapy

    Drug: Pembrolizumab
    Pembrolizumab
    Other Names:
  • MK-3475/pembrolizumab (KEYTRUDA®)
  • Radiation: Radiotherapy
    Radiotherapy - Standard Treatment

    Drug: Chemotherapy
    Chemotherapy - Standard Treatment

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. Acute toxicity as measured during treatment by CTCAE v4.0 [Up until 6 weeks after the end of chemoradiotherapy (week 14 of the study)]

    Secondary Outcome Measures

    1. The Progression Free Survival [Six months, one year and two years]

    2. The Overall Survival [Six months, one year and two years]

    3. To measure the duration of clinical benefit using RECIST [Six months, one year and two years]

    4. To evaluate late radiotherapy toxicities as measured during treatment by LENT SOMA [52 weeks from the end of radiation therapy (week 7)]

    Other Outcome Measures

    1. Identify biomarkers and correlate with clinical benefit, as defined by RECIST v1.1 [through study completion (24 months)]

    2. Analysis of circulating free tumour DNA [Screening, week 3, week 9 and week 15]

    3. Immunohistochemical analysis to identify immune infiltrates [through study completion (24 months)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Have treatment naive and histologically confirmed high-/intermediate-risk LA-SCCHN

    2. Be willing and able to provide written informed consent for the trial.

    3. Be > or = 18 years of age on day of signing informed consent.

    4. Have measurable disease based on RECIST 1.1.

    5. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumour lesion.

    6. Have a performance status of 0 or 1 on the ECOG Performance Scale.

    7. Be fit for definitive platin-based chemoradiation therapy.

    8. Demonstrate adequate organ function as defined in table 1, all screening labs should be performed within 10 days of confirmation of study eligibility.

    9. 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.

    10. 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.

    11. 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.

    Exclusion Criteria:
    1. 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.

    2. Has received prior radiotherapy to the head and neck region.

    3. 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.

    4. Has had a prior monoclonal antibody, chemotherapy, targeted small molecule therapy, or radiation therapy.

    5. 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.

    6. 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.

    7. 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.

    8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

    9. Has an active infection requiring systemic therapy.

    10. Has active tuberculosis.

    11. Has known hypersensitivity to pembrolizumab or any of its excipients.

    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 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.

    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, 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).

    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 prior to the first dose of trial treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Royal Marsden Hospital NHS Foundation Trust London United Kingdom SW3 6JJ

    Sponsors and Collaborators

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

    Investigators

    • Study Director: Prof Kevin Harrington, CTU, Consultant Clinical Oncologist

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Royal Marsden NHS Foundation Trust
    ClinicalTrials.gov Identifier:
    NCT02819752
    Other Study ID Numbers:
    • CCR4325
    First Posted:
    Jun 30, 2016
    Last Update Posted:
    Jan 13, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Royal Marsden NHS Foundation Trust
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 13, 2022