Chemotherapy + Robotic Surgery for Throat Cancer

(NECTORS Trial)

Overseen By Elizabeth Beaubien

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nader Sadeghi

Must not be taking: Taxanes, Cisplatin

Disqualifiers: Advanced T4 cancer, N3 disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for throat cancer linked to HPV (human papillomavirus). Instead of the usual chemo-radiotherapy, which often causes serious side effects, the trial tests chemotherapy with Docetaxel followed by robotic surgery to determine if it is more effective and causes fewer long-term issues. The goal is to improve cure rates and quality of life for patients. Suitable candidates have a specific type of newly diagnosed throat cancer that has not spread to distant parts of the body. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in cancer care.

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.

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

Research has shown that the chemotherapy drug docetaxel is generally well-tolerated by patients with certain types of cancer. In one study, only 0.6% of patients with normal liver function died due to treatment. However, some patients experienced disease progression during treatment.

Studies indicate that Transoral Robotic Surgery (TORS) is widely used and considered safe. The risk of serious complications is very low, similar to traditional surgery, making TORS usually well-tolerated by patients.

While both treatments appear safe, potential trial participants should discuss any concerns with their healthcare provider. This discussion will help them understand the risks and benefits based on their personal health situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with robotic surgery for throat cancer because it offers a precise and less invasive approach. Unlike traditional surgery, transoral robotic surgery allows for targeted removal of cancer tissue with minimal damage to surrounding areas, potentially leading to quicker recovery times and fewer complications. Additionally, using Docetaxel and Cisplatin, or sometimes Carboplatin, before surgery aims to shrink tumors, making them easier to remove and possibly enhancing overall treatment effectiveness. This approach represents a promising shift from conventional methods, which typically involve more invasive surgeries and a longer recovery period.

What evidence suggests that chemotherapy followed by robotic surgery is effective for throat cancer?

In this trial, participants will receive neoadjuvant chemotherapy with docetaxel, a chemotherapy drug that studies have shown to be effective in treating head and neck cancers, with success rates between 33% and 44%. Transoral robotic surgery and neck dissection will follow this treatment. Research suggests that using chemotherapy before the main treatment, combined with surgery through the mouth and neck surgery, has been successful for patients with more advanced throat cancer. This approach aims to provide a strong alternative to traditional chemo-radiotherapy treatments, which fail 20% of the time and can cause serious long-term side effects. The goal is for this new treatment to reduce failure rates to less than 10% and improve patients' quality of life by avoiding radiotherapy in most cases. ^{6 7 8 9 10}

Who Is on the Research Team?

Nader Sadeghi, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Transoral Robotic Surgery

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

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

Approved in European Union as Taxotere for:

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

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 is an effective chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, 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 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]

Citations

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Neoadjuvant Chemotherapy and Transoral Robotic ... In this study, neoadjuvant chemotherapy followed by transoral robotic surgery and neck dissection was an effective treatment option for patients with stage III ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04277858

Neoadjuvant Chemotherapy and Transoral Robotic ... The study hypothesis is that treatment with upfront (neoadjuvant) chemotherapy followed by transoral surgery and neck dissection is highly effective treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9682030/

Surgical clinical trials for HPV-positive oropharyngeal ... In this review, we summarize and discuss the past and current clinical trials involving surgery in the treatment of HPV-positive OPSCC.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02760667

Induction Chemotherapy Followed by Surgery for Locally ... The objective of this study is to assess the efficacy of induction chemotherapy followed by transoral surgical treatment and neck dissection, in definitive ...

5. withpower.com withpower.com/trial/phase-3-carcinoma-7-2018-1b059

Chemotherapy + Robotic Surgery 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8622087/

Docetaxel: an active drug for squamous cell carcinoma of the ... Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression ...

7. cancernetwork.com cancernetwork.com/view/a-phase-2-study-of-docetaxel-and-capecitabine-in-advanced-squamous-cell-carcinoma-of-the-head-and-neck

A Phase 2 Study of Docetaxel and Capecitabine in ... Patients who present with advanced-stage disease that is unresectable have a 5-year survival rate of 30% as compared with 60% to 98% 5-year ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01932697

NCT01932697 | Radiation Therapy and Docetaxel in ... This phase II trial studies how well radiation therapy and docetaxel work in treating patients with human papillomavirus (HPV)-related oropharyngeal cancer.

9. news-medical.net news-medical.net/health/Docetaxel-(Taxotere)-Head-and-Neck-Cancer.aspx

Docetaxel (Taxotere) Head and Neck Cancer The results demonstrated a significantly greater increase in progression-free survival in the TPF group than in the PF group, at a median of 11.4 versus 8.3 ...

10. products.sanofi.us products.sanofi.us/taxotere/taxotere.html

TAXOTERE® (docetaxel) injection, for intravenous use Among patients dosed at 60 mg/m2, mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with ...