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

NCT ID: NCT02707588

Last Updated: 2023-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-18
• Study Completion Date: 2022-10-17

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.

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab and radiotherapy

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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).

Radiotherapy

Intervention Type: 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).

Cetuximab and radiotherapy

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.

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: 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).

Radiotherapy

Intervention Type: 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).

Interventions

Pembrolizumab

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).

Intervention Type: DRUG

Cetuximab

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).

Intervention Type: DRUG

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).

Intervention Type: RADIATION

Other Intervention Names

antibody; antibody; Conventional Radiotherapy

Eligibility Criteria

Inclusion Criteria

1. Written informed consent

2. Age ≥18 ≤ 80 years.

3. Performance Status ECOG 0-1

4. 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

5. Availability of pre-treatment tumour tissue (for biomarker analysis, PD -L1, TILs and immune-monitoring)

6. p16 expression from tumor sample (immunohistochemistry)

7. Recording of the smoking history

8. No viral infection (HIV, Hepatitis B/C)

9. No autoimmune disease

10. No immunodeficiency or immunosuppressive therapy

11. No active CNS disease

12. No interstitial lung disease

13. No active infection

14. Women of child-bearing potential: negative serum pregnancy test at screening and use of appropriate contraception methods from study entry

15. Patients not proposed cisplatin-based chemotherapy because of age, general condition, if medically unfit or patient refusal.

16. Adequate organ laboratory values

17. Health insurance coverage

Exclusion Criteria

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers;

2. Squamous cell cancer involving cervical neck nodes with unknown primary site;

3. Metastatic disease;

4. 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;

5. Weight loss of >10% during the last 3 weeks prior the screening visit;

6. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol;

7. Concomitant treatment with any drug on the prohibited medication list such as live vaccines (for details, see the protocol);

8. History of another malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas);

9. If female, pregnant or lactating;

10. 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.

11. Known hypersensitivity reaction to study medication;

12. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupe Oncologie Radiotherapie Tete et Cou

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Pr BOURHIS, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Centre Guillaume le conquérant

Le Havre, , France

Countries

France

Other Identifiers

GORTEC 2015-01

Identifier Type: -

Identifier Source: org_study_id