Chemotherapy + Robotic Surgery for Throat Cancer

(NECTORS Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Nader Sadeghi

Must not be taking: Taxanes, Cisplatin

Disqualifiers: Advanced T4 cancer, N3 disease, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for advanced throat cancer caused by HPV. It uses chemotherapy first, then a precise robotic surgery to remove the cancer. This method aims to reduce the severe side effects of traditional treatments and improve patients' quality of life. Transoral robotic surgery (TORS) has become an accepted initial treatment for T1 and T2 head and neck squamous cell carcinoma (HNSCC).

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are receiving any other investigational agent, you cannot participate in this study.

What data supports the effectiveness of the treatment for throat cancer?

Research shows that docetaxel, a drug used in the treatment, has been effective in treating head and neck cancers, with response rates of 33% to 44% when combined with other drugs like cisplatin. Additionally, adding docetaxel to other treatments has improved survival rates and quality of life for patients with advanced head and neck cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy and robotic surgery for throat cancer safe?

Docetaxel, a chemotherapy drug used in various cancers, has been studied for safety in head and neck cancer. It can cause severe neutropenia (a drop in white blood cells), but alternate dosing schedules may reduce this risk. Safety data for robotic surgery specifically in throat cancer is not provided in the available research. ^{1 2 6 7 8}

What makes the chemotherapy and robotic surgery treatment for throat cancer unique?

This treatment combines docetaxel, a drug known for its effectiveness in head and neck cancers, with robotic surgery, which may offer more precision and less invasive procedures compared to traditional surgery. This combination could potentially enhance treatment outcomes by leveraging the strengths of both chemotherapy and advanced surgical techniques. ^{1 3 5 7 9}

Research Team

Nader Sadeghi, MD

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Eligibility Criteria

This trial is for adults over 18 with HPV-related oropharyngeal cancer (cancer in parts of the throat like tonsils and tongue), who are fit for surgery, have not had previous treatments, and no distant spread of cancer. They must be able to perform daily activities mostly without aid (Karnofsky >60% or ECOG <2) and agree to use contraception.

Inclusion Criteria

Agree to use effective contraception while on the study. Women of child bearing potential must have a negative pregnancy test, and not be lactating.

Signed study specific consent form

My throat cancer is p16 positive.

Exclusion Criteria

My advanced cancer cannot be surgically removed without losing organ function.

I currently have an infection.

I have had head or neck cancer before, but not skin cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive Docetaxel and Cisplatin (or Carboplatin) for 3 cycles

9 weeks

Transoral Robotic Surgery and Neck Dissection

Participants undergo transoral robotic surgery and neck dissection as definitive treatment

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 3, 6, and 12 months

Treatment Details

Interventions

• Docetaxel (Anti-mitotic Agent)
• Transoral Robotic Surgery (Procedure)

Trial Overview The study tests if chemotherapy followed by Transoral Robotic Surgery (TORS) can effectively treat oropharyngeal cancer with fewer side effects than current chemo-radiotherapy methods. The goal is a high cure rate with less than a 10% failure rate, avoiding radiotherapy in most cases.

Participant Groups

Group I: Neoadjuvant chemotherapy and surgery Experimental Treatment 1 Intervention

Docetaxel and Cisplatin x 3 cycles followed by Transoral robotic surgery and neck dissection. Carboplatin may be used instead of Cisplatin.

Docetaxel is already approved in Canada, Japan for the following indications:

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Nader Sadeghi

Lead Sponsor

Trials

1

Recruited

60+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Dr. Lucie Opatrny

McGill University Health Centre/Research Institute of the McGill University Health Centre

President and Executive Director since 2023

MDCM and Master's in Epidemiology and Biostatistics from McGill University, Master's in Healthcare Management and Diploma in Advanced Negotiation from Harvard University

Dr. Patrizia Cavazzoni

McGill University Health Centre/Research Institute of the McGill University Health Centre

Chief Medical Officer

MD from McGill University, residency in Psychiatry and fellowship in Mood Disorders at the University of Ottawa

Findings from Research

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 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]

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 phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

The combination of docetaxel and cisplatin showed a 46% objective response rate in patients with locally advanced or metastatic squamous-cell carcinoma of the head and neck, indicating significant efficacy in treating this type of cancer.

However, the treatment was associated with substantial toxicity, including severe neutropenia and gastrointestinal issues, and did not demonstrate any advantages over conventional treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma of the head and neck: a phase II study of the Southern Italy Cooperative Oncology Group (SICOG). Caponigro, F., Massa, E., Manzione, L., et al.[2020]

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

In a phase II study involving 43 patients with advanced head and neck cancer, docetaxel demonstrated a response rate of 32%, indicating its efficacy as a treatment option for this type of cancer.

The treatment was associated with significant side effects, including alopecia in 90% of patients and grade 3-4 neutropenia in 61% of treatment courses, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Catimel, G., Verweij, J., Mattijssen, V., et al.[2020]

Docetaxel demonstrated a significant growth-inhibiting effect on human tumor xenografts derived from head and neck squamous cell carcinoma (HNSCC) at a well-tolerated dose of 20 mg/kg, administered in two intravenous injections a week apart.

The study found that HNSCC tumors were less sensitive to cisplatin, indicating that docetaxel and cisplatin do not have cross-reactivity, suggesting that docetaxel could be a promising treatment option for HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The growth inhibiting effect of docetaxel (Taxotere) in head and neck squamous cell carcinoma xenografts. Braakhuis, BJ., Kegel, A., Welters, MJ.[2019]

References

1. 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]

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. 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]

4. England pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). [2022]

5. England pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma of the head and neck: a phase II study of the Southern Italy Cooperative Oncology Group (SICOG). [2020]

6. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

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

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. [2018]

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

Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. [2020]

9. Ireland pubmed.ncbi.nlm.nih.gov

The growth inhibiting effect of docetaxel (Taxotere) in head and neck squamous cell carcinoma xenografts. [2019]