Immunotherapy + Chemotherapy for Nasal and Sinus Cancer

Overseen By Renata Ferrarotto

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Prior anti-cancer therapy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for nasal and sinus cancer, specifically squamous cell carcinoma. The researchers aim to determine if using pembrolizumab (an immunotherapy drug), docetaxel, and either cisplatin or carboplatin (both chemotherapy drugs) together can effectively treat this cancer in stages II to IVb. The goal is to assess how well these medicines work together and if they can improve patient outcomes. Individuals newly diagnosed with this type of cancer who have not yet received treatment are ideal candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic anti-cancer therapy for this type of cancer.

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

Research shows that the combination of pembrolizumab, docetaxel, and either cisplatin or carboplatin is generally well-tolerated. A study on patients with laryngeal cancer using these drugs reported manageable side effects. Common side effects included mouth sores and changes in kidney function, but these occurred less frequently with docetaxel.

Pembrolizumab, already approved for some cancers, has an acceptable safety record in many cases. Research on its use with chemotherapy for nasal and sinus cancer indicates safe usage, though patients should be monitored for side effects. Anyone considering joining a trial should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for nasal and sinus cancer, which often involves surgery, radiation, and traditional chemotherapy, the combination treatment of pembrolizumab with chemotherapy drugs like docetaxel, cisplatin, or carboplatin offers a unique approach. Pembrolizumab is an immunotherapy drug that works by targeting the PD-1 pathway, effectively helping the immune system recognize and attack cancer cells. This mechanism is different from traditional chemotherapies that directly kill cancer cells but can also harm healthy cells. Researchers are excited because this combination has the potential to enhance the body's natural defenses against cancer while possibly reducing the side effects associated with typical chemotherapy regimens.

What evidence suggests that this treatment might be an effective treatment for nasal and sinus cancer?

Research has shown that combining pembrolizumab with chemotherapy drugs like docetaxel and either cisplatin or carboplatin may help treat certain cancers. In this trial, participants will receive a combination of pembrolizumab, docetaxel, and either cisplatin or carboplatin. Studies have found that this combination can lead to more patients experiencing tumor shrinkage or disappearance. For example, these drugs have worked well together in treating laryngeal cancer. Although data for nasal and sinus cancer is limited, the success in similar cancers suggests potential effectiveness. Pembrolizumab is known to help the immune system fight cancer cells, enhancing the potential benefits of this treatment mix. ^{2 4 6 7 8}

Who Is on the Research Team?

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with newly diagnosed, untreated Stage II-IVb squamous cell carcinoma of the nasal cavity/paranasal sinuses. Participants must have measurable disease, provide a tissue sample, not be pregnant or breastfeeding, agree to use contraception and have good organ function. Excludes those who've had prior cancer treatments for PNS SCC or immunotherapy.

Inclusion Criteria

I agree to follow the specified contraception guidelines and not donate sperm for 150 days after my last treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

My recent blood tests show my organs are functioning well.

Exclusion Criteria

I have been treated with specific immune therapy drugs before.

I haven't had cancer treatment or radiation for PNS SCC, but may have for other cancers over 2 years ago.

A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive pembrolizumab combined with induction chemotherapy (docetaxel and cisplatin or carboplatin) prior to radiation

6-8 weeks

Chemoradiation

Participants undergo chemoradiation therapy following induction chemotherapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Pembrolizumab

Trial Overview The trial is testing a combination therapy (PDC) involving pembrolizumab (an immunotherapy drug) and chemotherapy drugs docetaxel and either cisplatin or carboplatin in patients with advanced squamous cancer of the nasal cavity/paranasal sinuses.

How Is the Trial Designed?

Group I: pembrolizumab, docetaxel, and cisplatin or carboplatin Experimental Treatment 4 Interventions

IV

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 7 patients with advanced sinonasal squamous cell carcinoma, a modified TPF regimen combined with radiotherapy resulted in a complete response in all patients, indicating high efficacy of this treatment approach.

Despite some severe side effects like grade 4 leukopenia and neutropenia in a few patients, the overall safety profile was acceptable, with an impressive 85.7% disease-free survival rate at 60 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Study of Chemoradiotherapy Using Modified Docetaxel, Cis-diaminodichloroplatinum, and 5-Fluorouracil for Sinonasal Squamous Cell Carcinoma. Katagiri, K., Shiga, K., Saito, D., et al.[2022]

Docetaxel shows comparable efficacy to paclitaxel in treating ovarian cancer, with a median progression-free survival of 16 months and a low neurotoxicity rate of 5%, significantly lower than the over 30% seen with paclitaxel.

In a large randomized trial involving 1077 patients, docetaxel combined with carboplatin demonstrated acceptable toxicity and treatment adherence, justifying further analysis of its safety and efficacy compared to the traditional paclitaxel-carboplatin regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of docetaxel into first-line chemotherapy for ovarian cancer. Kaye, SB.[2019]

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving multiple patients.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: Trial data and implications for clinical management. Belani, C., Lynch, T.[2019]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

In a study of 54 patients with squamous cell carcinoma of the maxillary sinus, superselective cisplatin infusion combined with radiotherapy resulted in a 5-year overall survival rate of 67.9% and a local progression-free survival rate of 65.8%.

The treatment was associated with manageable toxicity, as no patients died from treatment-related complications, although some experienced late adverse effects like osteonecrosis and visual problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. Homma, A., Sakashita, T., Yoshida, D., et al.[2022]

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving various patient populations.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management. Belani, C., Lynch, T.[2018]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

A 91-year-old woman with advanced maxillary sinus carcinoma achieved a complete response to treatment after receiving chemoradiotherapy combined with intra-arterial docetaxel, showing no residual tumor in biopsy and CT scans post-treatment.

Twenty-one months after the treatment, the patient remained free of recurrence and metastasis, suggesting that this method could be an effective option for treating maxillary sinus squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of a 91-year-old woman with maxillary sinus carcinoma who achieved a complete response to chemoradiotherapy with intra-arterial administration of docetaxel]. Watanabe, A., Taniguchi, M., Kawabori, S.[2018]

The RADPLAT treatment strategy, which combines neoadjuvant selective intra-arterial cisplatin with concurrent radiation therapy, resulted in an impressive 5-year overall survival rate of 81% and a progression-free survival rate of 67% in 11 patients with advanced sinonasal malignancies.

This approach appears to be safe and effective, providing high response rates and excellent local control for patients with T3 and T4 disease, suggesting a promising option for improving outcomes in a typically high-mortality cancer group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of advanced sinonasal malignancies with pre-operative intra-arterial cisplatin and concurrent radiation. Madison Michael, L., Sorenson, JM., Samant, S., et al.[2018]

In a study involving six patients with maxillary sinus cancer, superselective cisplatin infusion via the ophthalmic artery, combined with radiotherapy, resulted in a complete response and no locoregional recurrences.

However, this treatment approach led to visual acuity loss in four out of six patients, indicating a significant risk that must be considered when using this method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ligation of the ethmoid arteries in superselective intra-arterial infusion of cisplatin for advanced maxillary sinus cancer fed by the ophthalmic artery. Tamagawa, K., Shinomiya, H., Okada, T., et al.[2023]

In a retrospective analysis of 371 patients with primary squamous cell carcinomas of the pyriform sinus, those who received multiple-agent chemotherapy had higher survival rates compared to those treated with single-agent chemotherapy.

The study suggests that induction chemotherapy may enhance survival in pyriform sinus cancers, but further prospective studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of survival after induction chemotherapy in pyriform sinus carcinoma. Brasnu, D., Fabre, A., Menard, M., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04030455?term=AREA%5BConditionSearch%5D(%22Laryngeal%20Squamous%20Cell%20Carcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Pembrolizumab%22)&rank=3

Cisplatin, Docetaxel, and Pembrolizumab in Treating ... This phase II trial studies how well cisplatin, docetaxel, and pembrolizumab work in treating patients with stage II-III laryngeal cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05027633

NCT05027633 | Immunotherapy With Chemotherapy and ... -Increase overall response rate (ORR), following pembrolizumab combined with induction chemotherapy prior to radiation, from historical 60% with induction ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596330/

Clinical Review - Pembrolizumab (Keytruda) - NCBI - NIH The predicted 5-year survival rate is 12% for mTNBC compared to 77% for all TNBC and 89% for all breast cancer.-. The standard approach for mTNBC is treatment ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/31/9/1636/761257/Pembrolizumab-with-Chemotherapy-for-Patients-with

Pembrolizumab with Chemotherapy for Patients with ... Effective, tailored treatments are urgently needed, yet recurrent or metastatic (R/M) SNSCC is excluded from prospective head and neck cancer clinical trials.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e18006

Comparative efficacy of pembrolizumab with carboplatin ... Conclusions: This NMA with MAIC suggests patients treated with the KNB10 regimen had improved or comparable ORR outcomes versus other ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05027633

Study Details | NCT05027633 | Immunotherapy With ... This is a single arm phase II study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (PDC) as single treatment ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11590380/

Safety outcomes of pembrolizumab with platinum agent ... Mucositis and elevated creatinine rates were significantly reduced within the taxane arm. Keywords: Metastatic head and neck cancer, oral cancer, ...

8. careacross.com careacross.com/clinical-trials/trial/NCT05925491

Pembrolizumab in Locally Advanced Sinonasal Carcinoma This study will test the Safety and activity of pembrolizumab plus chemotherapy as neoadjuvant treatment in locally advanced sinonasal undifferentiated ...