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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of the immunotherapy drug nivolumab and two chemotherapy drugs, carboplatin and paclitaxel, can effectively shrink HPV-negative head and neck cancers. It targets individuals with advanced cancer in areas such as the mouth, throat, or sinuses who have not previously received radiation or chemotherapy for this condition. Participants should have measurable cancer and no significant other health issues. The goal is to determine if this drug combination can control the disease more effectively than standard treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab, a type of immunotherapy, usually causes fewer severe side effects than standard treatments for some head and neck cancers. In one study, only 13.1% of patients experienced serious side effects, compared to 35.1% with other treatments, indicating that nivolumab is generally well-tolerated.

Studies indicate that using carboplatin and paclitaxel together is safe and manageable for patients with head and neck cancer. One study found this combination to be well-tolerated, offering promise for treating difficult cases. Another study showed that combining these drugs with a different immunotherapy also resulted in manageable side effects.

Overall, these treatments have been shown to be safe for most people, with side effects that can usually be managed. However, treatments can affect everyone differently. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which typically involve surgery, radiation, and chemotherapy, this approach combines standard chemotherapy drugs, Carboplatin and Paclitaxel, with Nivolumab, an immunotherapy drug. Nivolumab stands out because it works by boosting the body's immune system to better recognize and attack cancer cells, a method that traditional chemotherapy doesn't employ. Researchers are excited about this combination because it could potentially enhance the effectiveness of treatment by tackling the cancer from two different angles: directly targeting cancer cells with chemotherapy and empowering the immune system with Nivolumab. This dual approach may offer improved outcomes and potentially fewer side effects compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that nivolumab, a type of immunotherapy, can improve outcomes for patients with certain head and neck cancers. In previous studies, patients treated with nivolumab had a 67% chance of their cancer not worsening after one year and an 83% chance of surviving, suggesting it helps control cancer growth and boosts survival rates. Nivolumab also tends to cause fewer severe side effects than standard treatments.

In this trial, participants will receive either standard chemotherapy or de-escalated chemotherapy. When combined with carboplatin and paclitaxel, two chemotherapy drugs, the treatment has been effective in improving patient responses. The combination of paclitaxel and carboplatin has shown a 39% overall response rate in patients, with some experiencing complete or partial reduction in cancer. These drugs work well together to fight head and neck cancer by attacking cancer cells in different ways. ^{3 4 6 7 8}

Who Is on the Research Team?

Everett Vokes, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02625

Pembrolizumab Plus Carboplatin and Paclitaxel as First- ... Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00176267

Paclitaxel, Carboplatin And Low Dose Radiation As ... This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41203-9/fulltext

Long-term outcomes with concurrent carboplatin, paclitaxel ... Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

5. blogs.the-hospitalist.org blogs.the-hospitalist.org/content/carboplatin-radiosensitizing-agent-locally-advanced-head-and-neck-cancer-friendly-older

Carboplatin as a Radiosensitizing Agent in Locally ... The mean number of weekly carboplatin doses held was 0.3. 7 patients (27%) had at least one dose held. 21 (81%) patients showed treatment ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... Conclusion: Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26423341/

Safety and efficacy of concurrent carboplatin plus ... Concurrent carboplatin plus radiotherapy is tolerated and may be an option in treating locally advanced squamous cell carcinoma of the head and neck patients.

8. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/2796301

Cetuximab-Based vs Carboplatin ... After propensity score–based inverse probability weighting, treatment with carboplatin was associated with 15% improved overall survival ...