NCT03723967

FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel

Multicenter Prospective Single Arm Phase II Study Evaluating Efficacy & Safety of Durvalumab With Carboplatin/Paclitaxel as First Line Treatment in Patients With Recurrent/Metastatic SCCHN Not Eligible to Standard Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of the phase II trial is to determine the efficacy and safety of a combination of Durvalumab with the Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy.

Detailed description

For recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN), the standard first-line treatment is chemotherapy by cisplatin-fluorouracil and cetuximab which allows a median overall survival of 10.1 months. Due to its toxicity, this combination could be proposed only to patients younger than 70 years, good PS (ECOG PS0 or PS1) and adequate renal function. In routine practice it is estimated that the proportion of eligible patients is about two third. One third of patients were ineligible to first-line chemotherapy by cisplatin-fluorouracil-cetuximab. Among them, 25% due to PS2 and the others for various reasons (older than 70 years, renal insufficiency….). For these ineligible patients, an alternative chemotherapy should be proposed. The carboplatin-paclitaxel scheme with weekly paclitaxel is safe for poor population and demonstrated efficacy in head and neck cancers with overall survival varying from 4.9 months to 12.8 months in first line. The response rate varies from 20% to 52% and is about 25% in our experience. Even for frail patients it should be a safe and active treatment. Nivolumab, a monoclonal antibody targeting PD1 demonstrated survival benefit compared with chemotherapy in patients with SCCHN who progressed after platinum-based first line (median OS of 7.5 months versus 5.1 months and 12-month OS rate of 36.0% versus 16.6%). Safety data confirm these antibodies are of interest in a population of frail patients. Only 58.9% of patients experienced treatment-related adverse events with nivolumab arm and 13% of grade 3/4. Durvalumab, an anti-PDL1 antibody is currently tested in SCCHN with promising results. Head and neck cancers are rapidly progressive and due to the delayed action of immunotherapy, and the recent demonstration that immunotherapy with anti-PD1 or anti-PDL1 can be responsible of hyperprogression, patients will probably benefit from addition of chemotherapy to immunotherapy, mostly for patients unfit for cisplatin-fluorouracil because their poor condition is often related to the cancer and a rapid response is needed. This trial proposes to study the addition of Durvalumab to chemotherapy in first line treatment for frail patients with recurrent/metastatic SCCHN. Prior to this evaluation, a run-in tolerance study in a limited number of patients to ensure that the experimental treatment combination is safe.

Conditions

• Squamous Cell Carcinoma of the Head and Neck

Interventions

Type	Name	Description
DRUG	Durvalumab with Carboplatin/Paclitaxel	Durvalumab associated with Carboplatin / Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy

Timeline

• Start date: 2019-05-16
• Primary completion: 2020-05-16
• Completion: 2024-03-09
• First posted: 2018-10-30
• Last updated: 2024-04-22

Locations

17 sites across 1 country: France