Pre-Surgery Chemotherapy + Surgery & Radiation for Sinus Cancer

Recruiting at 148 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering chemotherapy before surgery and radiation therapy is more effective than surgery and radiation alone for individuals with nasal and paranasal sinus cancer. The chemotherapy drugs—docetaxel, cisplatin, and carboplatin—aim to shrink the tumor and reduce the amount of healthy tissue removed during surgery. Participants will either receive surgery and radiation alone or chemotherapy before surgery and radiation. This trial may suit individuals diagnosed with sinus cancer requiring surgery involving the eye socket or skull base. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the combination of docetaxel, cisplatin, and carboplatin is generally well-tolerated by patients. One study found that using these drugs together before other treatments helped patients with certain cancers live longer. Most participants in the study found the treatment safe, with side effects similar to those of other cancer treatments.

Common side effects included nausea and tiredness, but most patients managed these effectively. The drugs have been tested in various situations and are known for their ability to shrink tumors. While some patients might experience more serious side effects, these are less common and are closely monitored by doctors.

The current phase of this trial suggests confidence in the safety of these drugs based on earlier studies. However, ongoing research continues to ensure they remain safe for wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for sinus cancer because they integrate chemotherapy, surgery, and radiation therapy in a novel way. Unlike the standard approach, which generally involves surgery followed by radiation or chemotherapy, this trial evaluates the impact of combining chemotherapy with surgery and radiation more strategically. Arm A focuses on using cisplatin or carboplatin with radiation after surgery for patients with specific cancer characteristics. Arm B uniquely introduces docetaxel alongside cisplatin or carboplatin before surgery, aiming to shrink tumors and make surgery more effective. By exploring these combinations, the trial aims to improve outcomes and minimize the chances of cancer returning, offering hope for more effective management of sinus cancer.

What evidence suggests that this trial's treatments could be effective for sinus cancer?

This trial will compare two treatment approaches for sinus cancer. In one arm, participants will receive chemotherapy with docetaxel, cisplatin, or carboplatin before surgery and radiation. Research has shown that using these chemotherapy drugs before surgery and radiation can effectively treat sinus cancer. Specifically, one study found that this approach improved survival rates over three years compared to standard treatment. This combination helps shrink tumors, making surgery easier and more successful. Patients with head and neck cancers have responded well to these drugs, with some experiencing significant tumor reduction. The goal is to make the cancer easier to remove and control its spread with fewer side effects. ^{3 6 7 8 9}

Who Is on the Research Team?

Nabil Saba

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9630958/

Sinonasal Squamous Cell Carcinoma Survival Outcomes ... Induction therapy was safe and effective. When compared with SOC, induction therapy improved 3-year overall survival.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00003908?draw=2&rank=1

S9902 Docetaxel Plus Carboplatin in Treating Patients ... PURPOSE: Phase II trial to study the effectiveness of docetaxel plus carboplatin in treating patients who have metastatic or recurrent head and neck cancer.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hed.28177?af=R

Paranasal Sinus and Nasal Cavity Cancers: Systematic ... Tumors of the paranasal sinus and nasal cavity (PNS/NC) are rare and exhibit diverse histology, anatomic subsite, and malignant potential.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419385473

Empowering induction therapy for locally advanced head ... CRT has been shown to significantly improve overall survival (OS), progression-free survival (PFS), and/or local disease control compared with radiotherapy (RT) ...

5. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/484185

Rate of Pathologic Complete Responses to Docetaxel, ... As a single agent, it has produced response rates of 21% to 42% in patients with locally advanced, recurrent, and/or metastatic disease. The most significant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7304541/

Outcomes and Toxicities of Definitive Radiation ... Proton therapy (PT) improves outcomes in nasal cavity (NC) and paranasal sinus (PNS) cancers. We present the largest series utilizing intensity-modulated ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04521-6/pdf

442P Comparative outcomes of docetaxel plus cisplatin ... This retrospective analysis compares the efficacy and safety of two commonly used chemo regimens: docetaxel plus cisplatin (DP) versus paclitaxel plus.

8. clinicaltrial.be clinicaltrial.be/en/details/75921?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Docetaxel, Cisplatin and Fluorouracil in Treating Patient... INDUCTION CHEMOTHERAPY: Patients receive docetaxel intravenously (IV) over 1 hour on day 1, cisplatin IV over 30-180 minutes or carboplatin IV ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0385814608001879

The efficacy and safety of concurrent chemoradiotherapy ... Goepfert et al23 previously reported that 11 of 26 patients achieved disease-free status at 24 months. Nishimura et al14 reported promising CCRT results showing ...