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Squamous Cell Carcinoma of the Head and NeckPhase 2PembroRadNCT02707588

Tolerance and Efficacy of Pembrolizumab or Cetuximab Combined With RT in Patients With Locally Advanced HNSCC

A Phase 2 study testing Pembrolizumab, Cetuximab and Radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Groupe Oncologie Radiotherapie Tete et Cou at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The general aim of the study is to evaluate the anti-tumour activity and the tolerance profile of Pembrolizumab + RT in comparison to cetuximab + RT in patients with locally advanced HNSCC and to explore potential correlations between treatment outcome and the immune landscape. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Pembrolizumab, Cetuximab and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
133 participants
Where
1 siteFrance
Study dates
18 May 2016to 17 Oct 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent
  • Age ≥18 ≤ 80 years.
  • Performance Status ECOG 0-1
  • Histologically confirmed diagnosis of previously untreated locally advanced HNSCC (Stage III, IVa and IVb according to the American Joint Committee on Cancer Staging System) of one or more of the following sites: oral cavity, oropharynx, hypopharynx and larynx
  • Availability of pre-treatment tumour tissue (for biomarker analysis, PD -L1, TILs and immune-monitoring)
  • p16 expression from tumor sample (immunohistochemistry)
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  • Recording of the smoking history
  • No viral infection (HIV, Hepatitis B/C)
  • No autoimmune disease
  • No immunodeficiency or immunosuppressive therapy
  • No active CNS disease
  • No interstitial lung disease
  • No active infection
  • Women of child-bearing potential: negative serum pregnancy test at screening and use of appropriate contraception methods from study entry
  • Patients not proposed cisplatin-based chemotherapy because of age, general condition, if medically unfit or patient refusal.
  • Adequate organ laboratory values
  • Health insurance coverage

Who cannot join

  • Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers;
  • Squamous cell cancer involving cervical neck nodes with unknown primary site;
  • Metastatic disease;
  • Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent;
  • Weight loss of >10% during the last 3 weeks prior the screening visit;
  • Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol;
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  • Concomitant treatment with any drug on the prohibited medication list such as live vaccines (for details, see the protocol);
  • History of another malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas);
  • If female, pregnant or lactating;
  • Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial.
  • Known hypersensitivity reaction to study medication;
  • Any social, personal, medical and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Centre Guillaume le conquérant

    Le Havre, 76000

Other trials in France

About this study

Official title: A Phase II Randomized Study to Determine the Tolerance and Efficacy of Pembrolizumab or Cetuximab Combined With Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

The general aim of the study is to evaluate the anti-tumour activity and the tolerance profile of Pembrolizumab + RT in comparison to cetuximab + RT in patients with locally advanced HNSCC and to explore potential correlations between treatment outcome and the immune landscape.

Read the detailed description

A majority of HNSCC are locally advanced and commonly treated with concomitant chemo-radiotherapy (CT-RT). However, a large proportion of patients with locally advanced stage are not suitable for receiving cisplatinum-based chemotherapy (CT) concomitant with radiotherapy (RT) either due to age, general and/or medical condition(s).

An alternative standard treatment has been established, combining RT and cetuximab.

However, both CT-RT and cetuximab-RT which are considered as standard approaches in locally advanced non operated HNSCC are associated with poor outcome in patients with the most advanced T stage (T4) and/or N stage (>=N2) and/or HPV negative tumours. A new and promising approach could target immune response.

Pembrolizumab is a high-affinity monoclonal anti-PD1 antibody which showed antitumor activity in melanoma and NSCLC. In the KEYNOTE-012 (multi-center, nonrandomized Phase Ib HNSCC), Pembrolizumab was well tolerated and safe with no serious drug related AEs reported. About 51% (26/51) of patients had decreased tumor burden which was seen both in HPV (-) and HPV(+) HNSCC.

This observation led to the hypothesis generated in the current study that Pembrolizumab is potentially a very active drug in HNSCC and that the combination of Pembrolizumab with radiotherapy will be well tolerated, given the very good toxicity profile of the drug and will improve the outcome of patients with locally advanced HNSCC non suitable for CT-RT, as compared to the treatment of reference combining cetuximab and RT.

Being tested
Pembrolizumab, Cetuximab, Radiotherapy
Keywords
Determine the tolerance and efficacy of Pembrolizumab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called antibody

    200mg IV infusion every 3 weeks, i.e. on day 1, 22, 43 during the course of radiotherapy.

    Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions).

  • CetuximabDrug

    Also called antibody

    Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of radiotherapy.

    Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions).

  • RadiotherapyRadiation

    Also called Conventional Radiotherapy

    Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions).

Study groups in NCT02707588
Study groupRoleWhat they receive
Pembrolizumab and radiotherapyExperimental200 mg IV infusion every 3 weeks, i.e. on day 1, 22, 43 during the course of radiotherapy
Receives: Drug: Pembrolizumab; Radiation: Radiotherapy
Cetuximab and radiotherapyActive comparatorLoading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of radiotherapy.
Receives: Drug: Cetuximab; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Locoregional Control

    To compare between the 2 arms the rate of patients achieving Locoregional Control (LRC) at 15 months from the end of radiation therapy

    Measured: 15 months from the end of radiation therapy

Secondary outcomes (9)

  1. Progression free survival

    Minimum time from randomization to progression/relapse at any site (local, regional or distant) as defined by RECIST 1.1 criteria or to death from any cause. Patients who don't have any of these events are censored at the date of last follow-up.

    Measured: At 24 months after treatment initiation

  2. Locoregional progression and distant metastasis

    To estimate the respective contribution of locoregional progression, distant progression and death as first event in the progression-free survival, the cumulative incidences of these three types of events were calculated within a competing risk framework.

    Measured: At 24 months after treatment initiation

  3. Overall survival

    Time to death from any cause measured from randomization.

    Measured: At 24 months after treatment initiation

  4. Acute adverse events

    According to NCI-CTCAE version 4, the maximal grade of each toxicity observed during immune-radiotherapy will be used. All grades of toxicity will be tabulated by type of toxicity and by treatment arm.

    Measured: At 24 months after treatment initiation

  5. Delayed toxicity According to RTOG late toxicity scale

    According to RTOG late toxicity scale

    Measured: At 24 months after treatment initiation

  6. Duration of the feeding tube dependence

    It will be presented by treatment arm and analysed by Student t-test.

    Measured: At 24 months after treatment initiation

  7. Compliance to Pembrolizumab and Cetuximab

    Insufficient compliance to cetuximab or Pembrolizumab is defined as a patient receiving less than 75% of the planned dose, even if the dose reduction is due to toxicity

    Measured: At 24 months after treatment initiation

  8. Health related quality of life (QL)

    Assessment by EORTC QLQ-C30 and H\&N35 questionnaires

    Measured: At 24 months after treatment initiation

  9. Impact of p16 / HPV tumor status on the efficacy of the 2 regimens in patients with oropharyngeal initial tumor

    Assessment by CISH DNA method

    Measured: At 24 months after treatment initiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2016 (estimated)
  2. Study start18 May 2016
  3. Primary completionOct 2022
  4. Study completion17 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02707588
Sponsor's protocol ID
GORTEC 2015-01
Acronym
PembroRad
Status last verified
Aug 2022
First submitted
29 Feb 2016
Last updated
28 Feb 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Cetuximab and Radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Groupe Oncologie Radiotherapie Tete et Cou at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Locoregional Control (time frame: 15 months from the end of radiation therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02707588.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.

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