Cetuximab Therapeutic Drug Monitoring in Squamous Cell Carcinoma Head and Neck Cancer Patients: Determination of the Predictive Value Exposure Levels Through a Single Arm Multicentric Study (CETUXIMAX)

Only about 30 percent of cancer patients have a clinical benefit upon cetuximab administration. Pilot studies in colorectal and head and neck cancer patients have suggested that cetuximab pharmacokinetics (PK), i.e. clearance values, could impact on clinical outcomes such as survival.

Determining cetuximab plasma clearance requires sophisticated PK modeling using population approaches, thus making it difficult to implement in routine clinical practice. In addition, all the preliminary studies with cetuximab were based upon Elisa determination of cetuximab plasma levels, an analytical method that fails to meet the requirements of daily practice in laboratories performing therapeutic drug monitoring. This pilot study aimed at evaluating the mass spec method analytical performance as part of a " real life " study, evaluating the inter-patient variability of exposure levels in head and neck cancer patients, and establishing a putative link between those exposure levels and clinical outcome. Results from 25 patients fully confirmed the analytical performance of the mass spec method (e.g., lack of matrix effect, acceptable sensitivity to monitor trough levels, lack of impact of sampling processing or freezing/thawing cycles). In addition, a large inter-individual variability (Superior at 50 percent) was observed, both in the peak concentrations (Cmax) and in trough levels (Cmin). Most interestingly, despite the limited number of patients enrolled, a statistically significant association was shown between exposure levels (i.e. calculated AUC) and clinical outcome (DCR). This difference was even more significant on Cmin, thus suggesting that simple trough levels monitoring could help to predict efficacy. Further analysis on survival showed that although not statistically significant, a trend towards longer both progression-free survival and overall survival was observed in the subgroup of patients with higher trough levels. In particular, 3-year survival was 29 percent and 0 percent in the subgroups with high and low trough concentrations, respectively (unpublished data).

Beyond tumoral factors, these preliminary data suggest that cetuximab Cmin levels could be a predictive marker of therapeutic efficacy and that simple therapeutic drug monitoring could help to forecast clinical outcome or enable dosage adaptation.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Biological: Blood samples

• Study Type: Observational
• Enrollment (Anticipated): 122

Contacts and Locations

• Study Contact: Name: Sébastien SALAS, PU-PH; Phone Number: +33 491385708; Email: sebastien.salas@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Sébastien SALAS, PU-PH; Phone Number: +33 491385708; Email: sebastien.salas@ap-hm.fr
    • Principal Investigator: Sébastien SALAS, PU-PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patient with recurrent or metastatic histologically proven head and neck Squamous Cell Carcinoma. Patients will be treated by standard treatment as part of routine clinical practice

Description

Inclusion Criteria:

• Patients aged 18 to 75 years.
• Adult patient with recurrent or metastatic histologically proven head and neck Squamous Cell Carcinoma.
• Patients to be treated by standard treatment: chemotherapy with cisplatin or carboplatin and fluorouracil in combination with a cetuximab-based protocol
• Patients having signed the non-opposition form

Exclusion Criteria:

• Patient currently participating in or having participated to a study with another investigational agent.
• Patients minor
• Pregnant or breast-feeding women.
• Any contra-indication in the Second Primary Cancers

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patient with head and neck cancer; Patients treated by standard treatment and have a minimum of 4 blood samples.	Biological: Blood samples; A minimum of 4 blood samples and a maximum of 6 blood samples will be collected. Venous return blood samples collected as part of routine monitoring of patients for bioclinical parameters. Samples will be collected before start of the infusion and end of the infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Disease control rate (DCR) will be defined as the combination of complete response, partial response, and stable disease.	16 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Jean-Olivier ARNAUD, Dirctor, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2019
• Primary Completion (Anticipated): April 28, 2022
• Study Completion (Anticipated): April 28, 2022

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): January 6, 2020
• Last Update Submitted That Met QC Criteria: January 2, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Squamous Cell
• Other Study ID Numbers: 2019-36; Id RCB (Registry Identifier: 2018-A00771-54)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No