Pre-Surgery Chemotherapy + Surgery & Radiation for Sinus Cancer

Recruiting at 139 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: Investigational agents

Disqualifiers: Distant metastases, Leptomeningeal disease, Uncontrolled illnesses, 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: 37

82 Participants Needed

Trial Summary

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

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on investigational agents or have uncontrolled illnesses that interfere with the trial.

What data supports the effectiveness of this treatment for sinus cancer?

Research shows that using cisplatin and docetaxel together is effective for head and neck cancers, including sinus cancer, with some patients achieving complete response. Additionally, neoadjuvant chemoradiation (chemotherapy and radiation before surgery) with cisplatin or carboplatin followed by surgery has been effective for maxillary sinus cancer, with cisplatin showing a higher complete response rate. ^{1 2 3 4 5}

Is the combination of docetaxel and cisplatin safe for humans?

The combination of docetaxel and cisplatin has been studied in patients with head and neck cancer and non-small cell lung cancer, showing it is generally well-tolerated. Neutropenia (a low level of white blood cells) is the main side effect, but severe nerve damage and kidney problems are uncommon. ^{1 4 6 7 8}

What makes the pre-surgery chemotherapy treatment for sinus cancer unique?

This treatment is unique because it combines pre-surgery chemotherapy with carboplatin, cisplatin, and docetaxel, followed by surgery and radiation, which is not a standard approach for sinus cancer. The combination of these drugs is known to be effective in head and neck cancers, and using them together before surgery may enhance treatment outcomes. ^{1 2 4 9 10}

What is the purpose of this trial?

This randomized phase II trial studies how well chemotherapy before surgery and radiation therapy works compared to surgery and radiation therapy alone in treating patients with nasal and paranasal sinus cancer that can be removed by surgery. Drugs used in chemotherapy, such as docetaxel, cisplatin, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy before surgery and radiation therapy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and treated with radiation.

Research Team

Nabil Saba

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with nasal and paranasal sinus cancer that can be surgically removed. They should not have had prior radiation for head or neck tumors, no severe allergies to the chemo drugs used, and no other cancers in the last 2 years (except certain skin cancers). Participants need functioning major organs, no serious illnesses that could affect treatment, and women must not be pregnant.

Inclusion Criteria

My cancer can be measured and I've had a scan within the last 2 weeks.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the range allowing for eligibility, must be obtained < 2 weeks prior to randomization

Total bilirubin within normal limits (must be obtained =< 2 weeks prior to randomization)

Exclusion Criteria

I do not have cancer that has spread far or to the lining of my brain.

I have not had radiation for tumors in my head, neck, skull base, or brain.

I do not have any other serious illnesses that would stop me from receiving cancer treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Patients receive docetaxel and cisplatin or carboplatin every 21 days for up to 3 courses

9 weeks

3 visits (in-person)

Surgery

Patients undergo standard of care surgery

1 week

1 visit (in-person)

Post-operative Radiation

Patients undergo image guided intensity modulated radiation therapy (IMRT) for 30 fractions

6 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months if < 2 years from study entry, then every 6 months if 2-5 years from study entry

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Image Guided Radiation Therapy
• Intensity-Modulated Radiation Therapy
• Therapeutic Conventional Surgery

Trial Overview The study compares two approaches: one group receives chemotherapy (docetaxel, cisplatin, carboplatin) before surgery and radiation therapy; the other has surgery followed by radiation only. The goal is to see if pre-surgery chemo makes tumors smaller and reduces how much normal tissue needs removal.

Participant Groups

Group I: Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT) Experimental Treatment 8 Interventions

Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (surgery, IMRT, cisplatin, carboplatin) Active Control 7 Interventions

Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Neoadjuvant platinum-based radiochemotherapy (RCT) followed by radical surgery shows a 5-year overall survival rate of 35% in patients with advanced maxillary sinus squamous cell carcinoma, indicating its effectiveness as a treatment approach.

Cisplatin was associated with a higher complete response rate compared to carboplatin, although the overall survival rates between the two treatments were not significantly different.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation in squamous cell carcinoma of the maxillary sinus: a 26-year experience. Kreppel, M., Danscheid, S., Scheer, M., et al.[2021]

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]

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]

A patient with an advanced ethmoidal carcinoma that had spread to the brain showed significant tumor regression after treatment with Cis-dichlorodiamine platinum, despite previous radiation and chemotherapy not being effective.

This case suggests that preoperative chemotherapy with Cis-dichlorodiamine platinum could be beneficial for managing paranasal sinus carcinomas with intracranial extension, potentially improving surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Craniofacial resection following chemotherapy. Arbit, E., Sundaresan, N., Galicich, JH., et al.[2016]

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, 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]

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]

In a study of 106 patients with maxillary sinus squamous cell cancer treated between 1971 and 1987, combination therapy including preoperative radiation and chemotherapy followed by surgery resulted in 5-year survival rates of approximately 69% for the earlier period and 72% for the later period, showing consistent efficacy over time.

For a select group of 21 patients in the later period who received additional chemotherapy, the survival rates improved significantly to 85.7% at 5 years, indicating that enhanced treatment strategies can lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of long-term results of our combination therapy for squamous cell cancer of the maxillary sinus. Konno, A., Ishikawa, K., Terada, N., et al.[2019]

References

1. 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]

2. Egypt pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation in squamous cell carcinoma of the maxillary sinus: a 26-year experience. [2021]

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

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

Craniofacial resection following chemotherapy. [2016]

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. [2018]

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. [2019]

8. 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]

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

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

10. Norway pubmed.ncbi.nlm.nih.gov

Analysis of long-term results of our combination therapy for squamous cell cancer of the maxillary sinus. [2019]