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

NCT04218136 | Unknown

• 2 other identifiers: 2019-36ID RCB
• Study Type: observational
• Target: 122
• Locations: 1 country
• Sites: 1

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3-year survival was 29 percent and 0 percent in the subgroups with high and low trough concentrations, respectively (unpublished data).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.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  Disease control rate (DCR) will be defined as the combination of complete response, partial response, and stable disease.

  16 months

Study Arms (1)

patient with head and neck cancer

Patients treated by standard treatment and have a minimum of 4 blood samples.

Biological: Blood samples

Interventions

Blood samples BIOLOGICAL

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

patient with head and neck cancer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jean-Olivier ARNAUD, Dirctor

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Central Study Contacts

Sébastien SALAS, PU-PH

CONTACT

491385708; sebastien.salas@ap-hm.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 6, 2020
• Study Start: December 26, 2019
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: January 6, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)