NBTXR3 +/− Cetuximab for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
+253 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Johnson & Johnson Enterprise Innovation Inc.
Disqualifiers: Nasopharynx carcinoma, Non-squamous histology, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a global, open-label, randomized, 2-arm, Investigator's choice Phase 3 (Pivotal Stage) study to investigate the efficacy and safety of JNJ-90301900 (NBTXR3) / radiation therapy (RT)±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Cetuximab for head and neck cancer?
Research shows that adding Cetuximab to radiotherapy for head and neck cancer can extend the time the cancer is controlled and improve overall survival. In a study, patients receiving Cetuximab with radiotherapy had a longer median survival compared to those receiving radiotherapy alone.
12345Is the combination of NBTXR3 and Cetuximab safe for treating head and neck cancer?
NBTXR3 has been studied for safety in elderly patients with head and neck cancer, and Cetuximab is known to cause an acne-like rash in 70-80% of patients and can lead to serious allergic reactions. Both treatments have been used in head and neck cancer, but patients should be aware of these potential side effects.
16789What makes the treatment NBTXR3 unique for head and neck cancer?
NBTXR3 is unique because it involves the use of hafnium oxide nanoparticles that enhance the effects of radiation therapy, potentially making cancer cells more sensitive to treatment. This approach is different from traditional treatments that primarily rely on chemotherapy and radiation without the use of nanoparticles.
15101112Eligibility Criteria
This trial is for people aged 65 or older with a specific type of throat cancer (SCC) that hasn't been treated before. They must be able to handle radiation therapy, not have certain other health issues like severe allergies to cetuximab, HIV, active hepatitis B or C, heart problems, or lung disease. Women who are pregnant or nursing and those not using birth control can't join.Inclusion Criteria
My cancer is confirmed as squamous cell carcinoma in specific areas of the head or neck.
I can undergo radiation therapy with the goal of curing my condition.
My cancer is classified as T3-T4 or T2 with significant lymph node involvement.
+16 more
Exclusion Criteria
I do not have serious heart rhythm problems.
Subject participating in another clinical study at the time of signature of the informed consent form
My head or neck cancer has returned but I haven't had chemo or radiation for it.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
Treatment
Participants receive 70 Gy in 35 fractions over a 7 week period, with either RT alone or RT in combination with cetuximab
7 weeks
End of Treatment (EOT)
An EOT visit is performed 4 weeks after the completion of RT
4 weeks
Follow-up
Follow-up visits start at 12 weeks post-RT completion, continuing every 12 weeks for 2 years, then every 24 weeks thereafter until death or study end
48 months
Participant Groups
The study tests NBTXR3 combined with radiation therapy (RT), with or without the drug cetuximab. It's an open-label Phase 3 trial where patients are randomly assigned to one of two groups: one receiving NBTXR3/RT±cetuximab and the other receiving RT±cetuximab alone.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm AExperimental Treatment3 Interventions
JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33% of the Gross Tumor Volume.
Group II: Arm BActive Control2 Interventions
Investigator's choice of RT alone or RT in combination with cetuximab.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Radiation Oncology Medical Group - Laguna HillsLong Beach, CA
Hoag Hospital Newport BeachNewport Beach, CA
CHRISTUS - St. Vincent Regional Cancer CenterSanta Fe, NM
Herbert Irving Comprehensive Cancer CenterNew York, NY
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Johnson & Johnson Enterprise Innovation Inc.Lead Sponsor
NanobiotixLead Sponsor
References
Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model. [2018]Cetuximab (Cet), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is a standard of care in advanced head and neck (HN) cancer when combined with irradiation or cisplatin. The TPF association combining docetaxel (T), cisplatin (P) and fluorouracil (F) has become a chemotherapy of reference in the management of HN tumors. The aim of the study was to evaluate the anti-tumor activity of the association of Cet with TPF. In addition, the potential benefit from adding bevacizumab (Bev), an anti-VEGF monoclonal antibody, was examined.
Effects of the administration of epidermal growth factor receptor specific inhibitor cetuximab, alone and in combination with cisplatin, on proliferation and apoptosis of Hep-2 laryngeal cancer cells. [2019]Epidermal growth factor receptor (EGFR) overexpression and prognostic value in head and neck squamous cell cancer is the basis for targeting by anti-EGFR antibodies, which increase the efficacy of radiotherapy. In order to evaluate the best therapeutic schedule, the effects of cetuximab (C225) on Hep-2 cell proliferation, alone and in combination with cisplatin, were studied.
Cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2019]The majority of the head and neck cancers are squamous cell carcinomas, which commonly overexpress the EGF receptor (EGFR). Cetuximab is a chimeric monoclonal antibody that binds with high affinity to the extracellular domain of EGFR, and in addition induces antibody-dependent cellular cytoxicity. In a randomized Phase III trial in patients with locoregionally advanced squamous cell carcinoma of the head and neck, the addition of cetuximab to radiotherapy prolonged the median time of locoregional control from 14.9 to 24.4 months and increased the median overall survival from 29.3 to 49.0 months. In patients with platinum-refractory recurrent and/or metastatic disease, the objective response and disease-control rates in various studies ranged from 10 to 13% and from 46 to 56%, respectively. In the EXTREME trial, the addition of cetuximab to platinum/5-fluorouracil as first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck not only led to significant improvements in survival, response rate and disease control, but also induced a better symptom control in comparison with that observed with platinum/5-fluorouracil alone.
Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. [2023]The present meta-analysis was updated with randomized controlled trials (RCTs) to revaluate the efficacy and safety of cetuximab vs. cisplatin combined with radiotherapy in patients of head and neck squamous cell carcinoma (HNSCC).
The role of cetuximab in the management of head and neck cancers. [2020]The standard of care for patients with locally-advanced head and neck cancer is chemoradiation or surgical resection followed by radiation treatment with or without chemotherapy and despite aggressive, multimodality therapies with their associated toxicities, attempts are being made to improve efficacy while reducing toxicity. Cetuximab is a chimeric mAb directed against the EGFR that showed clinical activity in squamous cell carcinoma of head and neck (SCCHN).
Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. [2021]This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation.
The role of cetuximab in the treatment of squamous cell cancer of the head and neck. [2019]The epidermal growth factor receptor (EGFR) is a member of the HER family of tyrosine kinase growth factor receptors. Binding to EGFR by its natural ligands, mainly epidermal growth factor (EGF) or transforming growth factor (TGF)-alpha, results in a conformational change in the receptor, which promotes homo- or heterodimerisation or oligomerisation with other EGFR molecules or other HER family members. Dimerisation results in the activation of intracellular tyrosine kinase, autophosphorylation and activation of signal transduction molecules, ultimately leading to cell cycle progression, reduced apoptotic capacity, angiogenesis and the metastatic phenotype. EGFR is expressed on normal human cells and also across a range of malignancies. Tumour EGFR expression correlates with poor prognosis and resistance to therapy. Cetuximab is a chimeric human:murine monoclonal antibody that binds competitively to the EGFR. Binding of the antibody to the EGFR prevents activation of the receptor by endogenous ligands; proliferation is reduced, apoptosis enhanced, and angiogenesis, invasiveness and metastasis reduced. Binding of cetuximab to the receptor also results in internalisation and degradation of the antibody-receptor complex, downregulating EGFR expression. EGFR has been recognised as an important therapeutic target in cancer. Other antibodies are also in development, and small molecular inhibitors of the tyrosine kinase domain are available. Cetuximab adds to the activity of radiotherapy in locoregional head and neck cancer, and when given with platinum-based chemotherapy is active in a proportion of patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck, as is cetuximab monotherapy. When cetuximab is added to cisplatin monotherapy in the first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck, the objective response rate is significantly improved and the hazard ratio for progression is 0.78. The most commonly reported adverse event associated with cetuximab treatment is an acneiform rash that occurred in 70 - 80% of patients treated with cetuximab. Presence of the characteristic rash is significantly associated with response and/or survival. It is possible that development of acneiform rash may become an important clinical prognostic marker. Serious cetuximab-related toxicities include hypersensitivity reactions. Thus, cetuximab is biologically active across a range of clinical scenarios in squamous cell carcinoma of the head and neck. Ongoing studies will be important in establishing its role in the routine management of head and neck cancer.
Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. [2018]Although locally advanced head and neck squamous cell carcinoma (HNSCC) can be effectively treated using chemoradiotherapy (CRT) with docetaxel (DTX), and cisplatin (CDDP) plus 5-fluorouracil (TPF-CRT), severe adverse events (especially neutropenia) can limit treatment adherence. Therefore, we evaluated the safety and efficacy of a new chemotherapy regimen that consisted of DTX and CDDP plus cetuximab (Cmab) with concurrent radiotherapy.
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.
Cellular and molecular properties of (90)Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro. [2021]Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A″-DTPA) and radiolabeling with (90)Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI).
Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2021]Cetuximab is a monoclonal antibody able to inhibit and to degrade the transmembrane receptor Her-1, also known as epidermal growth factor receptor (EGFR). The inhibition of EGFR is of major importance since the receptor influences many important tumor cell activities including tumor growth, neo-angiogenesis, inhibition of the apoptotic response to chemotherapy and radiotherapy. Available experimental data suggest that cetuximab may enhance chemotherapy and radiotherapy activity, reverse resistance to some anticancer drugs and has itself anticancer activity Early clinical data support experimental results. This paper reviews the published experiences on cetuximab in the treatment of advanced head and neck cancer and points out the future objectives of the clinical research on this drug.
Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data. [2018]To review the current state of the data on the use of cetuximab in head and neck squamous cell carcinoma (HNSCC).