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

Head and Neck Cancer Clinical Trial

— CETUXIMAX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04218136
• Other study ID #: 2019-36
• Secondary ID: ID RCB
• Status: Recruiting
• Start date: December 26, 2019
• Est. completion date: April 28, 2022

Study information

• Verified date: January 2020
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Sébastien SALAS, PU-PH
• Phone: 491385708
• Email: sebastien.salas[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: April 28, 2022
• Est. primary completion date: April 28, 2022
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

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