NBTXR3 +/− Cetuximab for Head and Neck Cancer

Recruiting at 245 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Johnson & Johnson Enterprise Innovation Inc.

Disqualifiers: Nasopharynx carcinoma, Non-squamous histology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

500 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

What 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. ^{1 5 10 11 12}

Research Team

Johnson & Johnson Enterprise Innovation Inc Clinical trial

Principal Investigator

Johnson & Johnson Enterprise Innovation Inc.

Eligibility 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.

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.

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

Treatment Details

Interventions

• Cetuximab
• NBTXR3

Trial Overview 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.

Participant Groups

Group I: Arm A Experimental Treatment 3 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 B Active Control 2 Interventions

Investigator's choice of RT alone or RT in combination with cetuximab.

Who Is Running the Clinical Trial?

Johnson & Johnson Enterprise Innovation Inc.

Lead Sponsor

Trials

5

Recruited

910+

Nanobiotix

Lead Sponsor

Trials

7

Recruited

950+

Findings from Research

The combination of cetuximab (Cet) with the TPF chemotherapy regimen (docetaxel, cisplatin, and fluorouracil) significantly reduced tumor volume and improved histological responses in a mouse model of advanced head and neck cancer, indicating strong anti-tumor activity.

Adding bevacizumab (Bev) to the TPF-Cet combination did not provide additional benefits over the TPF-Cet treatment alone, suggesting that TPF-Cet is a highly effective option for managing advanced head and neck tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model. Bozec, A., Sudaka, A., Etienne-Grimaldi, MC., et al.[2018]

Cetuximab alone slightly inhibited the growth of Hep-2 cells but did not induce cell death, indicating limited efficacy on its own.

When combined with cisplatin, cetuximab significantly enhanced the inhibition of cell growth and increased apoptosis, suggesting that its clinical effectiveness may be more related to its ability to boost the effects of other pro-apoptotic treatments rather than just inhibiting cell repopulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Bussu, F., Pozzoli, G., Giglia, V., et al.[2019]

In a Phase III trial, adding cetuximab to radiotherapy for locoregionally advanced squamous cell carcinoma of the head and neck significantly improved median locoregional control from 14.9 to 24.4 months and overall survival from 29.3 to 49.0 months.

For patients with platinum-refractory recurrent or metastatic disease, cetuximab combined with platinum/5-fluorouracil showed improved survival, response rates (10-13%), and disease control (46-56%), along with better symptom management compared to platinum/5-fluorouracil alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. Specenier, P., Vermorken, JB.[2019]

In a meta-analysis of seven randomized controlled trials, cetuximab combined with radiotherapy resulted in significantly poorer overall survival and locoregional control compared to cisplatin combined with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC).

While cetuximab showed inferior efficacy, the overall incidence of severe adverse events was similar between the cetuximab and cisplatin treatment groups, indicating that cetuximab may not provide a safety advantage despite its reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. Li, Y., Yang, C., Gan, Y., et al.[2023]

Cetuximab, a monoclonal antibody targeting the EGFR, has been shown to improve survival rates when used alongside radiation therapy for patients with locally-advanced head and neck cancer, as demonstrated in a landmark study.

In recurrent and metastatic cases, cetuximab also enhances the effectiveness of chemotherapy, indicating its significant role in the treatment of squamous cell carcinoma of the head and neck, although further research is needed to optimize its use and identify the best patient candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the management of head and neck cancers. Kabolizadeh, P., Kubicek, GJ., Heron, DE., et al.[2020]

The phase I study involving 19 elderly or frail patients with advanced head and neck cancer showed that the radioenhancer nanoparticles, NBTXR3, had a good safety profile, with no dose-limiting toxicities or serious adverse events related to the treatment.

NBTXR3 was successfully injected intratumorally and remained localized during radiation therapy, with preliminary signs of antitumor activity observed, indicating its potential for further evaluation in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hoffmann, C., Calugaru, V., Borcoman, E., et al.[2021]

Cetuximab is an effective treatment for squamous cell carcinoma of the head and neck, enhancing the effects of radiotherapy and improving response rates when combined with cisplatin chemotherapy, as indicated by a significant hazard ratio for progression of 0.78.

The most common side effect of cetuximab is an acneiform rash, which occurs in 70-80% of patients and may serve as a prognostic marker for treatment response and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Burtness, B.[2019]

The new chemotherapy regimen combining docetaxel, cisplatin, and cetuximab (B-CRT) for treating locally advanced head and neck squamous cell carcinoma resulted in severe neutropenia in 56% of patients, indicating significant safety concerns.

Due to the high incidence of adverse events, particularly neutropenia and leukopenia, the study was terminated early, and it remains unclear if B-CRT is as effective as the standard TPF-CRT regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. Nishimura, G., Taguchi, T., Takahashi, M., et al.[2018]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Conjugating cetuximab with CHX-A"-DTPA and radiolabeling it with (90)Yttrium does not change its ability to block cancer cell growth or its binding affinity to the EGFR, ensuring that its therapeutic function remains intact.

The combination of (90)Y-cetuximab with external-beam irradiation significantly enhances the inhibition of head and neck squamous cell carcinoma cell growth, suggesting a potential improvement in radiotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and molecular properties of (90)Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro. Saki, M., Toulany, M., Sihver, W., et al.[2021]

Cetuximab is a monoclonal antibody that effectively inhibits the epidermal growth factor receptor (EGFR), which plays a crucial role in tumor growth and resistance to treatments like chemotherapy and radiotherapy.

Clinical data suggest that cetuximab not only has its own anticancer effects but may also enhance the effectiveness of chemotherapy and radiotherapy in patients with advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. Merlano, M., Occelli, M.[2021]

Cetuximab, when combined with platinum-based chemotherapy, showed a higher overall response rate (34.2%) compared to platinum therapy alone (17.0%) in patients with recurrent/metastatic head and neck squamous cell carcinoma, indicating its potential to enhance treatment efficacy.

Despite the improved response rates, the aggregate analysis revealed no significant improvement in overall survival when comparing platinum-based therapy plus cetuximab to platinum therapy alone, suggesting that cetuximab should complement existing treatments rather than replace them until more conclusive data is available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data. Reeves, TD., Hill, EG., Armeson, KE., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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]

3. England pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the management of head and neck cancers. [2020]

6. England pubmed.ncbi.nlm.nih.gov

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]

7. England pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the treatment of squamous cell cancer of the head and neck. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Cellular and molecular properties of (90)Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data. [2018]