Clinical trial NCT04218136: 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
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Head and Neck Cancer
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
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

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Disease Control Rate
timeFrame: 16 months
Secondary outcomes:
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille
Study officials:
affiliation: Assistance Publique Hôpitaux de Marseille
name: Jean-Olivier ARNAUD, Dirctor
role: STUDY_DIRECTOR
References: