Immunotherapy + Chemotherapy for Nasal and Sinus Cancer

Overseen By Renata Ferrarotto

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a single arm phase II study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (PDC) as single treatment modality in patients with stage II-IVb (T2-4, any N, M0) squamous cell carcinoma of the nasal cavity/paranasal sinuses (PNS SCC).

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.

What data supports the effectiveness of the drug combination used in the Immunotherapy + Chemotherapy for Nasal and Sinus Cancer trial?

Research shows that the combination of docetaxel and cisplatin is effective in treating head and neck cancers, with response rates of 33% to 44% in recurrent cases and over 90% in initial treatments. Additionally, a case study reported a complete response in a patient with maxillary sinus carcinoma using docetaxel, suggesting its potential effectiveness in similar cancers. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy generally safe for humans?

The combination of docetaxel with cisplatin or carboplatin has been studied in various cancers and is generally well-tolerated, with neutropenia (low white blood cell count) being the main side effect. Severe neuropathy (nerve damage) and nephrotoxicity (kidney damage) are uncommon. Pembrolizumab combined with docetaxel has also been investigated for head and neck cancer, indicating a focus on safety in these studies. ^{4 6 7 8 9}

What makes the drug combination of Carboplatin, Cisplatin, Docetaxel, and Pembrolizumab unique for nasal and sinus cancer?

This treatment is unique because it combines immunotherapy (Pembrolizumab) with chemotherapy drugs (Carboplatin, Cisplatin, and Docetaxel), potentially enhancing the body's immune response to fight cancer while directly targeting cancer cells. This combination may offer a novel approach compared to traditional treatments that typically use chemotherapy or radiation alone. ^{1 4 10 11 12}

Research Team

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Cisplatin (Chemotherapy)
• Docetaxel (Chemotherapy)
• Pembrolizumab (Checkpoint Inhibitor)

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.

Participant Groups

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

IV

Carboplatin is already approved in Canada for the following indications:

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+

Findings from Research

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]

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 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 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, 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]

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]

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 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 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 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]

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]

References

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

The treatment of advanced sinonasal malignancies with pre-operative intra-arterial cisplatin and concurrent radiation. [2018]

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

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

3. Japan 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]. [2018]

4. England 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. [2020]

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

Preliminary Study of Chemoradiotherapy Using Modified Docetaxel, Cis-diaminodichloroplatinum, and 5-Fluorouracil for Sinonasal Squamous Cell Carcinoma. [2022]

6. United States 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. [2019]

7. United States 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. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

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

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

10. United States 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. [2022]

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

Analysis of survival after induction chemotherapy in pyriform sinus carcinoma. [2019]