Ficlatuzumab + Cetuximab for Head and Neck Cancer
(FIERCE-HN Trial)
Recruiting in Palo Alto (17 mi)
+101 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AVEO Pharmaceuticals, Inc.
Must be taking: Cetuximab
Disqualifiers: Severe allergies, Brain metastases, Cardiovascular disease, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to compare the efficacy and safety of ficlatuzumab plus cetuximab compared to placebo plus cetuximab in participants with recurrent/metastatic (R/M) HPV-negative Head and Neck Cancer.
The primary hypothesis is that ficlatuzumab combined with cetuximab is superior to cetuximab alone in terms of progression-free survival and/or overall survival.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, there is a 'washout period' (time without taking certain medications) required for prior treatments, which includes 2 weeks for chemotherapeutic agents and radiation therapy, and 3 weeks for antibody-drug conjugates.
What data supports the effectiveness of the drug combination Ficlatuzumab and Cetuximab for head and neck cancer?
Research shows that Cetuximab, when used with radiotherapy, improves outcomes for patients with advanced head and neck cancer without increasing side effects. Additionally, Cetuximab has been effective in treating other cancers, like colorectal cancer, by targeting specific cancer cell receptors.
12345What safety data exists for the treatment of Ficlatuzumab + Cetuximab in humans?
Cetuximab, used in combination with other treatments, has been associated with side effects like skin rash and nail infections. Some patients have experienced eye issues like corneal erosion (damage to the eye's surface) and trichomegaly (abnormal eyelash growth).
16789What makes the drug combination of Ficlatuzumab and Cetuximab unique for head and neck cancer?
The combination of Ficlatuzumab and Cetuximab is unique because it targets two pathways that are involved in cancer growth, potentially overcoming resistance to Cetuximab alone. Ficlatuzumab blocks the HGF/cMet pathway, while Cetuximab targets the EGFR pathway, making this combination promising for patients with cetuximab-resistant head and neck cancer.
13101112Eligibility Criteria
This trial is for adults over 18 with recurrent or metastatic HPV-negative head and neck squamous cell carcinoma who've had prior unsuccessful treatment with anti-PD-1/PD-L1 therapy and platinum-based chemo. They should be reasonably healthy (ECOG status of 0 or 1) and not pregnant, willing to use contraception, and have a measurable lesion that hasn't been treated by radiation unless it's clearly growing.Inclusion Criteria
You are capable of providing written consent and following the protocol guidelines.
You possess a feeding tube, thus making you eligible for the study.
I am 18 years old or older.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ficlatuzumab or placebo in combination with cetuximab every 28-day cycle
44 months
Visits on Day 1 and Day 15 of each 28-day cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days
Participant Groups
The study tests if ficlatuzumab combined with cetuximab improves survival compared to placebo plus cetuximab in patients whose cancer has returned or spread. It aims to see which combination is better at stopping the cancer from progressing.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab)Experimental Treatment2 Interventions
IV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle
Group II: Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab)Experimental Treatment2 Interventions
Intravenous (IV) ficlatuzumab dose A on Day 1 (D1) and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle
Group III: Arm 3 (Comparator Arm: placebo plus cetuximab)Placebo Group2 Interventions
IV placebo (saline, ficlatuzumab-matched) on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle
Cetuximab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Erbitux for:
- Locally or regionally advanced squamous cell carcinoma of the head and neck
- Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
- BRAF V600E mutation-positive metastatic colorectal cancer
🇪🇺 Approved in European Union as Erbitux for:
- Squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The George Washington UniversityWashington, United States
MD Anderson Cancer CenterHouston, TX
University of Kansas Cancer CenterWestwood, KS
University of Pittsburgh Medical Center - Hillman Cancer CenterPittsburgh, PA
More Trial Locations
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Who Is Running the Clinical Trial?
AVEO Pharmaceuticals, Inc.Lead Sponsor
References
Cetuximab. [2020]Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb) is a monoclonal antibody that binds to the epidermal growth factor receptor, which is important in the growth of many cancers. In February 2004, it was granted accelerated approval by the US FDA for the treatment of metastatic colorectal cancer on the basis of tumour response rates in Phase II trials.
Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? [2015]Radiotherapy remains the foundation of current treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). It has been shown that the addition of concurrent chemotherapy to radiotherapy (chemoradiotherapy, CRT, or chemotherapy-enhanced radiation therapy, CERT) results in improved clinical outcome in terms of both locoregional control and overall survival in some groups of patients. However, CRT is associated with severe, dose-limiting acute toxicities and, in some patients, a higher proportion of late toxicities. In addition, most CRT regimens are platinum-based and there is evidence that the maximum tolerable toxicity has been reached with the dose intensities currently used in bolus cisplatin regimens. Therefore, if we are to further improve outcomes through increased treatment compliance, more effective and more tolerable regimens are needed. Recent results from a phase III randomised study demonstrate that the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux)given concomitantly with radiotherapy yields a significant clinical benefit over radiotherapy alone without any increase in radiotherapy-associated toxicity. In this review, we explore the question of the degree to which adding cetuximab improves the efficacy of radiotherapy in locally advanced SCCHN and how the benefits of cetuximab plus radiotherapy compare with those achievable with CRT.
YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. [2021]Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC). This study addresses the need of biomarkers of treatment response to the EGFR-targeting antibody cetuximab (Erbitux®).
Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]Cetuximab (Erbitux(®)) is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR). In the USA, the approval of cetuximab has been recently expanded to include the first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer (mCRC) when used in combination with FOLFIRI (irinotecan, fluorouracil, leucovorin [folinic acid]). The addition of cetuximab to first-line treatment with FOLFIRI improved progression-free survival, overall survival, and objective response rates relative to treatment with FOLFIRI alone in patients with EGFR-expressing mCRC with KRAS wild-type tumors. Therefore, cetuximab plus FOLFIRI is a useful biomarker-directed option in the first-line treatment of this patient population.
TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck. [2023]Label="Objectives" NlmCategory="UNASSIGNED">The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy.
[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval.
Persisting corneal erosion under cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody). [2022]To report persisting corneal erosion and trichomegaly as ocular side effects of cetuximab (Erbitux) treatment, a monoclonal antibody against the epidermal growth factor (EGF) receptor.
Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes. [2022]The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes.
Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. [2021]EGFR is an established therapeutic target in head and neck squamous cell carcinoma (HNSCC). The EGFR-targeting monoclonal antibody cetuximab (Erbitux, Imclone Systems, Inc., Branchburg, USA) was FDA-approved for use in HNSCC in 2006. The molecular basis for the efficacy of an antibody approach compared with inhibition of EGFR tyrosine kinase function using small-molecule inhibitors, or downregulation of protein expression via antisense strategies, remains incompletely understood.
Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer. [2021]Cetuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9-11.4) and 8.9 (90% CI = 2.7-15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6-40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC.
[Monoclonal antibodies for the treatment of head and neck cancer]. [2018]Monoclonal antibodies are now part of the armamentarium available for the treatment of head and neck cancer. Cétuximab, a monoclonal antibody targeting EGFR, improves overall survival as compared with radiotherapy alone as radical treatment of locally advanced head and neck cancer. It is now reimbursed in Belgium after multidisciplinary discussion if cisplatin is contra-indicated. In the metastatic setting adding cétuximab to platinum based chemotherapy improves overall survival as compared with chemotherapy alone, a first-time event over a 30-year period, unfortunately not yet accessible to the Belgian patients. Other monoclonal antibodies targeting EGFR or VEGF are also currently under investigation while cétuximab is being explored in the induction, the maintenance or the post-operative radiotherapy settings.