Nivolumab + Chemotherapy for Head and Neck Cancer

(DEPEND Trial)

Overseen By Everett Vokes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Metastatic disease, Immunodeficiency, Active infection, others

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

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

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drug combination Nivolumab, Carboplatin, and Paclitaxel for head and neck cancer?

Research shows that using paclitaxel and carboplatin together can help treat advanced head and neck cancer, potentially improving survival and preserving organs. This suggests that adding Nivolumab, which is known to boost the immune system, might further enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Nivolumab, Carboplatin, and Paclitaxel safe for treating head and neck cancer?

The combination of Carboplatin and Paclitaxel has been studied in head and neck cancer, showing tolerable safety with some side effects like neutropenia (low white blood cell count) and neurotoxicity (nerve damage). No treatment-related deaths were reported in these studies, indicating a generally acceptable safety profile. ^{1 6 7 8 9}

How is the drug combination of Nivolumab, Carboplatin, and Paclitaxel unique for head and neck cancer?

This treatment is unique because it combines Nivolumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs Carboplatin and Paclitaxel, which kill cancer cells directly. Nivolumab has shown to improve survival in patients with head and neck cancer who have not responded to platinum-based chemotherapy, offering a new option beyond traditional chemotherapy alone. ^{3 10 11 12 13}

What is the purpose of this trial?

This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.

Research Team

Everett Vokes, MD

Principal Investigator

University of Chicago

Eligibility Criteria

Adults with advanced stage IV HPV-negative head and neck cancer, who haven't had chemotherapy or radiation for this condition. They must have a good performance status, normal organ function, no history of severe allergies to the drugs used in the trial, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

Total bilirubin ≤ 1.5 mg/dL

Absolute neutrophil count ≥ 1,500

My organs are functioning normally.

Exclusion Criteria

My cancer has spread to distant parts of my body.

The origin of my cancer is unknown.

I have not taken high-dose steroids or immunosuppressants in the last 7 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with nivolumab, carboplatin, and paclitaxel to assess tumor response

2-3 weeks

Multiple visits for treatment and monitoring

Chemoradiation

Participants receive risk-adapted chemoradiotherapy based on response to induction therapy

24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

24 months

Periodic visits for assessments

Treatment Details

Interventions

• Carboplatin
• Nivolumab
• Paclitaxel

Trial Overview The study is testing if nivolumab combined with carboplatin and paclitaxel can shrink cancers significantly in patients with advanced HPV-negative head and neck cancer before they receive other treatments like surgery or more chemo.

Participant Groups

Group I: Standard Chemotherapy Experimental Treatment 3 Interventions

Induction Therapy

Group II: De-escalated Chemotherapy Experimental Treatment 6 Interventions

Radiation therapy with chemotherapy

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall response rate, with 27% achieving complete responses, indicating significant efficacy in treating this patient population.

The maximum tolerated dose of paclitaxel was determined to be between 230 and 265 mg/m2, with manageable side effects, primarily grade 3/4 neutropenia and thrombocytopenia, suggesting that this treatment can be safely administered while potentially enhancing organ preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. Dunphy, F., Boyd, J., Dunleavy, T.[2015]

In a study of 62 patients with advanced head and neck carcinoma, induction chemotherapy with paclitaxel and carboplatin resulted in a 66% overall response rate, indicating significant efficacy in this challenging patient population, most of whom had Stage IV disease.

The treatment was well tolerated, and organ preservation was achieved in 45% of patients, highlighting the potential for maintaining quality of life while improving survival outcomes, particularly in responders with oropharyngeal and hypopharyngeal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999. Dunphy, FR., Dunleavy, TL., Harrison, BR., et al.[2015]

In a study of 27 patients with recurrent squamous cell carcinoma of the head and neck, the combination of paclitaxel and carboplatin showed an objective response rate of 29.6%, with a median response duration of 4.2 months.

However, the treatment was associated with significant toxicities, including high rates of neutropenia (62.9%) and other severe side effects, indicating a need for safer chemotherapy alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. Pivot, X., Cals, L., Cupissol, D., et al.[2017]

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

Weekly paclitaxel treatment in 74 patients with recurrent or metastatic head and neck cancer showed a 29% overall response rate, indicating promising efficacy in this challenging condition.

The treatment was associated with manageable side effects, with the most common severe adverse events being leukopenia and neutropenia, suggesting that while effective, careful monitoring of blood counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. Tahara, M., Minami, H., Hasegawa, Y., et al.[2015]

In a study of 18 patients with recurrent metastatic head and neck squamous cell carcinoma, the combination of cetuximab and paclitaxel after immune checkpoint inhibitor therapy showed a 44.4% objective response rate and a 72.2% disease control rate, indicating significant efficacy.

The treatment was associated with manageable safety, with some patients experiencing grade 3 adverse events like neutropenia, but no treatment-related deaths occurred, suggesting that this regimen is a viable option for patients who have progressed after ICI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Suzuki, S., Toyoma, S., Kawasaki, Y., et al.[2021]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

In a phase I/II study involving 28 patients with advanced head and neck carcinoma, the combination of escalating doses of paclitaxel and cisplatin resulted in a high overall response rate of 78%, with 13 complete responses and 8 partial responses.

The treatment was generally well-tolerated, with no dose-limiting hematologic toxicity observed, although some patients experienced mild to moderate side effects like paresthesia and myalgias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer. Hitt, R., Paz-Ares, L., Hidalgo, M., et al.[2015]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a phase 3 trial involving 361 patients with recurrent squamous-cell carcinoma of the head and neck, nivolumab significantly improved overall survival compared to standard therapy, with a median survival of 7.5 months versus 5.1 months.

Nivolumab also had a better safety profile, with fewer severe treatment-related adverse events (13.1% vs. 35.1% in standard therapy), and patients reported stable quality of life compared to those receiving standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. Ferris, RL., Blumenschein, G., Fayette, J., et al.[2022]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

In a phase III trial, patients with head and neck squamous cell carcinoma who were resistant to platinum-based chemotherapy and treated with nivolumab experienced a 30% lower risk of death compared to those receiving standard single-agent chemotherapy.

The 1-year survival rate for patients treated with nivolumab was twice that of those receiving traditional chemotherapy, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2021]

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

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer. [2015]

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

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. [2019]