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

NCT02707588 | Completed Phase 2 DMC

• 1 other identifier: GORTEC 2015-01
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Determine the tolerance and efficacy of Pembrolizumab

Outcome Measures

Primary Outcomes (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

  15 months from the end of radiation therapy

Secondary Outcomes (9)

• Progression free survival

  At 24 months after treatment initiation

• Locoregional progression and distant metastasis

  At 24 months after treatment initiation

• Overall survival

  At 24 months after treatment initiation

• Acute adverse events

  At 24 months after treatment initiation

• Delayed toxicity According to RTOG late toxicity scale

  At 24 months after treatment initiation

Study Arms (2)

Pembrolizumab and radiotherapy

EXPERIMENTAL

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

Drug: Pembrolizumab; Radiation: Radiotherapy

Cetuximab and radiotherapy

ACTIVE COMPARATOR

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.

Drug: Cetuximab; Radiation: Radiotherapy

Interventions

Pembrolizumab DRUG

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).

Also known as: antibody

Pembrolizumab and radiotherapy

Cetuximab DRUG

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).

Also known as: antibody

Cetuximab and radiotherapy

Radiotherapy RADIATION

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).

Also known as: Conventional Radiotherapy

Cetuximab and radiotherapy; Pembrolizumab and radiotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead

Study Sites (1)

Centre Guillaume le conquérant

Le Havre, 76000, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Antibodies; Cetuximab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Therapeutics

Study Officials

• Jean Pr BOURHIS, MD

  CHU Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Suisse

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: March 14, 2016
• Study Start: May 18, 2016
• Primary Completion: October 1, 2022
• Study Completion: October 17, 2022
• Last Updated: February 28, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)