EACH: Evaluating Avelumab in Combination With Cetuximab in Head and Neck Cancer

NCT03494322 | Completed Phase 2

• 1 other identifier: UCL/17/0560
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Head \& neck (H\&N) cancer is the eighth most common cancer in the UK. Advanced H\&N cancer which has come back after treatment or has spread to other parts of the body is incurable and the average life expectancy of these patients is less than a year. New drugs called immune checkpoint inhibitors work with the patient's own immune system to fight cancer. They are used in the clinic to treat a number of cancers, including H\&N cancer. It may be possible to make immune checkpoint inhibitors more effective by combining drugs that work in different ways. In effect, attacking the cancer from different angles. Cetuximab is a well-established drug that works by blocking signals that tell cancer cells to grow and divide into more cells. It also engages with the immune system within the tumour. The trial aims to see if giving cetuximab along with an immune checkpoint inhibitor drug called avelumab is better at treating advanced H\&N cancer than giving avelumab on its own. These two drugs have not been given together before, so to start with, the investigator plans to enrol a small number of patients and give the patients avelumab + cetuximab to make sure the combination is safe at the doses chosen. After this, the investigator plans to enrol 114 patients with advanced H\&N cancer. Half the patients will be treated with avelumab alone and the other half with avelumab + cetuximab. Both drugs are given intravenously in the hospital once every 2 weeks. Treatment lasts for up to a year and patients will be followed up for up to 2 years from the time they enter the study. Patients will be recruited from around 15 hospitals in the UK. Recruitment would be expected to start in the second quarter of 2018 and it will take about 29 months (Safety run-in: 5 months; Phase II: 24 months) to recruit all the patients.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety run-in: Occurrence of dose limiting toxicity

  Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Patients experiencing any of the following adverse events related to either cetuximab or avelumab during the DLT period will be considered to have experienced a DLT: * Any grade 3 or 4 adverse reaction requiring a dose reduction of cetuximab * Any adverse reaction resulting in a more than a 14 day treatment delay for any agent.

  From start of cycle 1 (each cycle is 28 days) upto six weeks.

• Phase II: Disease control rate at 24 weeks after randomisation

  Assessed using iRECIST

  From randomisation upto 24 weeks

Secondary Outcomes (9)

• Objective response (iCR or iPR) at 6 and 12 months

  6 months and 12 months after registration/randomisation

• Disease control at 6 and 12 months

  6 and 12 months after registration/randomisation

• Best overall response

  From start of treatment to 24 months after registration, or upto start date of a new treatment for their disease, whichever came first, assessed up to 24 months.

• Duration of response

  From the date of the first response assessment showing iCR or iPR to the date of the response assessment documenting iPD according to iRECIST, assessed up to 24 months.

• Overall survival

  Time from registration/randomisation to death from any cause, assessed up to 24 months.

Study Arms (2)

Avelumab + cetuximab

EXPERIMENTAL

Patients will receive treatment in 4-week cycles and treatment may continue for up to 1 year. Avelumab + cetuximab combination therapy: Cycle 1 * Day 1: Cetuximab 500\* mg/m2 given IV over approx 3 hrs * Day 15: Cetuximab 500\* mg/m2 given IV over approx 2 hrs + avelumab 10 mg/kg given IV over approx 1 hr All other cycles: \- Days 1 and 15: Cetuximab 500\* mg/m2 given IV over approx 2 hrs + avelumab 10 mg/kg given IV over approx 1 hr \*Cetuximab dose will be dependent on outcome of safety run-in. There must be a 60 minute break between the administration of cetuximab and avelumab.

Drug: Avelumab; Drug: Cetuximab

Avelumab monotherapy

OTHER

Patients will receive treatment in 4-week cycles and treatment may continue for up to 1 year. Avelumab monotherapy will be given as follows: All cycles Avelumab 10 mg/kg on days 1 and 15 given IV over approximately 1 hour

Drug: Avelumab

Interventions

Avelumab DRUG

Avelumab 10 mg/kg given IV

Avelumab + cetuximab; Avelumab monotherapy

Cetuximab DRUG

Cetuximab 500\* mg/m2 given IV \*Cetuximab dose will be dependent on outcome of safety run-in.

Avelumab + cetuximab

Eligibility Criteria

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

You may qualify if:

• Safety run in: Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma that is considered incurable by local therapies
• Phase II: Histologically/cytologically confirmed recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
• Prior treatment with a platinum agent (either for recurrent/metastatic disease; or as part of radical intent multimodality treatment if disease has recurred within 6 months). (NB: This criterion is not applicable for the safety run-in).
• No previous treatment with cetuximab for metastatic/recurrent disease
• Age ≥18 years
• WHO Performance Status 0 or 1
• Measurable disease according to RECIST v1.1
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• Adequate venous access for administration of treatment and collection blood samples for exploratory biological samples
• Willing to have a new biopsy (NB: This criterion is not applicable for the safety run-in).
• Life expectancy of \>3 months
• Women of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods from date of informed consent, which must be continued for 120 days after completion of trial treatment.
• Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options

You may not qualify if:

• Patients with undifferentiated nasopharyngeal or sino-nasal cancers.
• Disease suitable for treatment with curative intent.
• Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
• Treatment with any investigational agent within 4 weeks prior to the first dose of trial treatment.
• Anti-cancer monoclonal antibody therapy within 4 weeks prior to randomisation
• Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to randomisation.
• Persisting grade ≥2 toxicity related to prior therapy
• Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial.
• Women who are pregnant or breast feeding.
• Grade 3 or 4 peripheral neuropathy.
• Any serious and/or unstable pre-existing medical, psychiatric or other condition, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Patients who are not able to give informed consent for any reason.
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Hepatitis infection at screening
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.

Sponsors & Collaborators

• University College, London: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

University College Hospital

London, NW1 2PG, United Kingdom

Location

Related Publications (1)

• Ng K, Metcalf R, Sacco J, Kong A, Wheeler G, Forsyth S, Bhat R, Ward J, Ensell L, Lowe H, Spanswick V, Hartley J, White L, Lloyd-Dehler E, Forster M. Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK. BMJ Open. 2023 Nov 27;13(11):e070391. doi: 10.1136/bmjopen-2022-070391.

  PMID: 38011968 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

avelumab; Cetuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Martin Forster, FRCP PhD

  University College London Hospitals

  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

Model Details: Randomised phase II study with safety run in

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: April 11, 2018
• Study Start: July 20, 2018
• Primary Completion: September 15, 2021
• Study Completion: April 23, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-05

Locations

GB (1)