Ignite Creation Date:
2025-12-24 @ 5:54 PM
Ignite Modification Date:
2025-12-24 @ 5:54 PM
Study NCT ID:
NCT06725368
Status:
RECRUITING
Last Update Posted:
2025-12-23
First Post:
2024-11-28
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Carboplatin + Paclitaxel + Cetuximab (PCC) After Failure of Pembrolizumab +/- First-line Chemotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Sponsor:
Centre Paul Strauss
Organization:
Study Overview
Official Title:
Carboplatin + Paclitaxel + Cetuximab (PCC) After Failure of Pembrolizumab +/- First-line Chemotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: CARPACCIO (CARboplatin PAClitaxel Cetuximab IO Immuno-oncology)
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CARPACCIO
Brief Summary:
This study targets an adult population of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), who have failed after a first line of treatment with pembrolizumab associated or not with chemotherapy and having an indication for a second line of treatment. Patients will be recruited in France in medical oncology departments.
The main objective is to evaluate the objective response rate of PCC in patients with HNSCC with locoregional and/or distant 2nd line metastatic disease after failure of pembrolizumab +/- chemotherapy. The secondary objectives of the study are to evaluate other efficacy parameters by monitoring the progression of the disease, the tolerance of the treatment by collecting adverse effects and quality of life.
The duration of participation in the research is 12 months.
The main objective is to evaluate the objective response rate of PCC in patients with HNSCC with locoregional and/or distant 2nd line metastatic disease after failure of pembrolizumab +/- chemotherapy. The secondary objectives of the study are to evaluate other efficacy parameters by monitoring the progression of the disease, the tolerance of the treatment by collecting adverse effects and quality of life.
The duration of participation in the research is 12 months.
Detailed Description:
Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer worldwide.
First-line treatment was shaken up in 2019 by showing that a combination of platinum, 5-fluorouracil (5-FU) and the anti-cell death program-1 (PD-1) immunotherapy, pembrolizumab, improved significantly improved overall survival (OS) compared to the standard EXTREME regimen (platinum, 5-FU and cetuximab).
After this first line and in the absence of a randomized therapeutic trial, the therapeutic strategy is not known. Possible chemotherapies are paclitaxel or methotrexate.
Systemic treatment is indicated for patients with locoregional recurrence not eligible for radiotherapy or surgery with curative intent, or progression of distant metastatic disease.
Cetuximab is approved as a second-line treatment in the United States. For patients whose tumor progresses on pembrolizumab maintenance therapy with a platinum-free interval of at least 3 months, restarting platinum therapy is potentially effective. The combination of platinum with cetuximab and paclitaxel is then possible and potentially more effective than monotherapy, including in fragile patients.
The use of cetuximab in the second line appears all the more interesting since its use immediately after anti-PD-1 immunotherapy gives hope for a form of potentiation, as has been reported in several publications since 2020.
Very recently, the results of a French retrospective study evaluating the effectiveness of chemotherapy based on taxane + cetuximab +/- platinum in 99 patients with HNSCC tumor progression and locoregional or metastatic recurrence after immune checkpoint inhibitors was presented by the team of Peers from the Gustave Roussy Institute. They suggest that this combination was effective in this situation and deserved further investigation.
The only existing prospective study was reported during ASCO meeting in 2023. The Japanese team evaluated in a Phase II trial the efficacy of combining paclitaxel with cetuximab in 35 patients with R/M HNSCC after platinum-based chemotherapy and anti-PD1 immunotherapy. The ORR was 69.7%. The median progression-free survival was 5.6 months, and the overall survival was 13.4 months.
A multicenter retrospective study was presented at ESMO 2023. It analyzed the efficacy of paclitaxel alone (69 patients) and the combination of paclitaxel with cetuximab (83 patients) in patients with R/M HNSCC refractory to platinum-based chemotherapy, taxane-naive, and progressive under immune checkpoint inhibitors. An increase of ORR was assessed for the combination of paclitaxel and cetuximab. The median progression-free survival was 4.9 months, and the overall survival was 9.4 months.
Finally, in a study investigating the efficacy of paclitaxel and cetuximab in 57 patients with R/M HNSCC after failure of first-line treatment including an immune checkpoint inhibitor, the ORR was 47.4%. The median duration of response was 5.5 months and disease control was achieved in 42 patients, resulting in a DCR of 71.9%. The median PFS was 5.9 months and the median OS was 14.0 months. The 6-month PFS and OS rates were 48% and 74%, respectively.
First-line treatment was shaken up in 2019 by showing that a combination of platinum, 5-fluorouracil (5-FU) and the anti-cell death program-1 (PD-1) immunotherapy, pembrolizumab, improved significantly improved overall survival (OS) compared to the standard EXTREME regimen (platinum, 5-FU and cetuximab).
After this first line and in the absence of a randomized therapeutic trial, the therapeutic strategy is not known. Possible chemotherapies are paclitaxel or methotrexate.
Systemic treatment is indicated for patients with locoregional recurrence not eligible for radiotherapy or surgery with curative intent, or progression of distant metastatic disease.
Cetuximab is approved as a second-line treatment in the United States. For patients whose tumor progresses on pembrolizumab maintenance therapy with a platinum-free interval of at least 3 months, restarting platinum therapy is potentially effective. The combination of platinum with cetuximab and paclitaxel is then possible and potentially more effective than monotherapy, including in fragile patients.
The use of cetuximab in the second line appears all the more interesting since its use immediately after anti-PD-1 immunotherapy gives hope for a form of potentiation, as has been reported in several publications since 2020.
Very recently, the results of a French retrospective study evaluating the effectiveness of chemotherapy based on taxane + cetuximab +/- platinum in 99 patients with HNSCC tumor progression and locoregional or metastatic recurrence after immune checkpoint inhibitors was presented by the team of Peers from the Gustave Roussy Institute. They suggest that this combination was effective in this situation and deserved further investigation.
The only existing prospective study was reported during ASCO meeting in 2023. The Japanese team evaluated in a Phase II trial the efficacy of combining paclitaxel with cetuximab in 35 patients with R/M HNSCC after platinum-based chemotherapy and anti-PD1 immunotherapy. The ORR was 69.7%. The median progression-free survival was 5.6 months, and the overall survival was 13.4 months.
A multicenter retrospective study was presented at ESMO 2023. It analyzed the efficacy of paclitaxel alone (69 patients) and the combination of paclitaxel with cetuximab (83 patients) in patients with R/M HNSCC refractory to platinum-based chemotherapy, taxane-naive, and progressive under immune checkpoint inhibitors. An increase of ORR was assessed for the combination of paclitaxel and cetuximab. The median progression-free survival was 4.9 months, and the overall survival was 9.4 months.
Finally, in a study investigating the efficacy of paclitaxel and cetuximab in 57 patients with R/M HNSCC after failure of first-line treatment including an immune checkpoint inhibitor, the ORR was 47.4%. The median duration of response was 5.5 months and disease control was achieved in 42 patients, resulting in a DCR of 71.9%. The median PFS was 5.9 months and the median OS was 14.0 months. The 6-month PFS and OS rates were 48% and 74%, respectively.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: