NECTORS: Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharyngeal Cancer.

Sponsor

Nader Sadeghi (Other)

Overall Status

Recruiting

CT.gov ID

NCT04277858

Collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre (Other)

Enrollment

Location

Arm

120.5

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this trial is to study the efficacy of treatment of human papilloma virus (HPV) related oropharyngeal cancer with chemotherapy followed by Transoral Robotic Surgery (TORS) as definitive treatment. Current treatment of oropharyngeal cancer are chemo-radiotherapy. There is significant lifelong side effects associated with this approach related to tissue effects of radiotherapy. The side effects results in significant quality of life deterioration among the patients. Overall there is 20% failure rate with this treatment approach. The study hypothesis is that treatment with upfront (neoadjuvant) chemotherapy followed by transoral surgery and neck dissection is highly effective treatment allowing competitive cure rate compared to chemo-radiotherapy with less than 10% failure rate, while avoiding radiotherapy in majority of cases. It is also hypothesized that better functional and quality of life outcome maybe achieved with this approach.

Condition or Disease	Intervention/Treatment	Phase
Oropharynx Cancer Tonsil Cancer Throat Cancer Base of the Tongue Carcinoma	Drug: Docetaxel	Phase 2

Detailed Description

The current standard of care for advanced (AJCC-7 edition stage III and IV) oropharyngeal squamous cell carcinoma are concomitant chemoradiation, or surgery followed by adjuvant radiation therapy with or without concomitant chemotherapy. These approaches have persistent and significant lifelong side effects and sequelae related to treatment, and in particular related to radiotherapy. The side effects of radiotherapy (augmented with concomitant chemotherapy) include soft tissue fibrosis, loss of salivary function, dry mouth, life long disturbed taste function, poor dental health with rapidly decaying teeth, dysfunction of swallowing, significant loss of the mobility of the base of tongue and pharyngeal constrictors, loss of laryngeal elevation, esophageal stricture, and at times severe side effects such as soft tissue necrosis or osteoradionecrosis of the mandible. About 10% of the patients undergoing chemoradiation for oropharyngeal cancer develop long term swallowing dysfunction with feeding tube dependency. As a result , patient's quality of life (QOL) is adversely affected. Improvements in the side effect profile of treatment, the functional outcome, and the QOL remain very important areas of advancement in treating this patient population. Improvements in functional outcome need to be achieved while maintaining or improving the oncologic outcome and cure rates for cancer, compared to the standard of care.

Use of Taxane based chemotherapy along with Platinum drugs (Cisplatin and Carboplatin) in high dose neoadjuvant setting, coupled with Transoral Laser Microsurgery (TLM) or Transoral Robotic Assisted Surgery (TORS), allows potential for improved oncologic outcome as well as avoidance of long term sequelae of high dose radiation therapy to head and neck. These transoral surgical approaches (TLM and TORS) provide improved functional outcome compared with traditional open composite resections and complex reconstructive algorithms for oropharynx. TLM and TORS are currently in clinical use for early (stage T1 and T2 with N0 or N+ve) oropharyngeal cancer.

De-escalation treatment strategies of TORS followed by adjuvant radiotherapy are being investigated currently. However even without de-escalation there is overall 18-20% rate of treatment failure and half of failures are due to distant metastasis in the absence of loco-regional recurrence. In this study the investigators propose systemic escalation of treatment with neoadjuvant chemotherapy (docetaxel and cisplatin) followed by de-escalated locoregional treatment with transoral surgery and neck dissection reserving radiotherapy for salvage.

This approach has the potential for improved functional outcome by avoiding short and more importantly long term and permanent sequelae of radiation therapy in oropharyngeal cancer treatment. This approach is a new paradigm in treatment of oropharyngeal cancer, and can significantly improve the functional outcome of cancer treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

neoadjuvant Docetaxel and Cisplatin and transoral surgeryneoadjuvant Docetaxel and Cisplatin and transoral surgery

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study: Induction Chemotherapy Followed by Transoral Robotic Surgery and Neck Dissection for Definitive Management of Oropharyngeal Squamous Cell Carcinoma. (NECTORS Trial)

Actual Study Start Date :

Aug 14, 2018

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Aug 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant chemotherapy and surgery Docetaxel and Cisplatin x 3 cycles followed by Transoral robotic surgery and neck dissection. Carboplatin may be used instead of Cisplatin.	Drug: Docetaxel Subjects will be treated with neoadjuvant docetaxel and cisplatin for 3 cycles. This is followed by transoral robotic surgery (TORS) and neck dissection as definitive treatment, reserving radiotherapy for salvage. Other Names: Cisplatin, Transoral robotic surgery

Arm

Intervention/Treatment

Experimental: Neoadjuvant chemotherapy and surgery

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

Drug: Docetaxel

Subjects will be treated with neoadjuvant docetaxel and cisplatin for 3 cycles. This is followed by transoral robotic surgery (TORS) and neck dissection as definitive treatment, reserving radiotherapy for salvage.

Other Names:

Cisplatin, Transoral robotic surgery

Outcome Measures

Primary Outcome Measures

Primary outcome: progression free survival. [2 years]
Subjects will be evaluated for cancer recurrence or persistence. Index cancer recurrence or persistence following completion of treatment at any site will be recorded as an event. Progression free survival will be calculated at 2 years according to the Kaplan Meier methods.

Secondary Outcome Measures

Disease Specific Survival (DSS) [5 years]
The trial subjects will be followed for vital statistics (dead or alive) from the time enrolled in the trial. Any deaths that is caused by the index cancer will count as an event. DSS will be calculated with intention to treat analysis according to the Kaplan Meier methods at 5 years.
Overall Survival (OS) [5 years]
The trial subjects will be followed for vital statistics (dead or alive) from the time of enrolment. Death from any cause will be counted as an event. Overall survival will be calculated according to the Kaplan Meier methods at years.
General Quality of Life (QOL) [12 months.]
Patient-reported general quality of life outcome will be measured according to The European Organization for Research and Treatment of Cancer (EORTC) general quality of life questionnaire (EORTC QLQ-C30) at 3 month, 6 months, and 12 months following the completion of treatment. These questionnaires are validated and an integrated system for assessing the quality of life (QoL) of cancer patients participating in clinical trials. Outcome score for functional scales at 12 months will be compared to pretreatment levels.
Head and Neck Specific Quality of Life (QOL) [12 months]
Patient-reported quality of life outcome will be measured according to EORTC head and neck specific questionnaire (QLQ-H&N35) prior to trial treatment (baseline), at 3 month, 6 months, and 12 months following the completion of treatment. These questionnaires are validated and an integrated system for assessing the quality of life (QoL) of head and neck cancer patients participating in clinical trials. Outcomes for symptom scales in H&N-35 at 12 months will be compared to pretreatment levels.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Squamous cell cancer of oropharynx, p 16 positive
American Joint Commission on Cancer version-7 (AJCC-7) Stage III (T1N1, T2N1, T3N0, T3N1) and stage IVa (T1N2, T2N2, T3N2)
Treatment Naive
No evidence of distant metastatic disease
Fit for surgery, and primary tumor assessed surgically resectable with negative margins via transoral approach
Age > 18 years
Karnofsky performance status > 60% or Eastern Cooperative Oncology Group (ECOG) < 2
Absolute neutrophil count (ANC) > 2,000, platelets > 100,000 and calculated creatinine clearance > 50 cc/min
Signed study specific consent form
No other malignancies except cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) within the last 5 years
Agree to use effective contraception while on the study. Women of child bearing potential must have a negative pregnancy test, and not be lactating.

Exclusion Criteria:

Patients with advanced T4 cancer unresectable without organ preservation
P16 negative tumor
N3 disease (Stage IVB AJCC-7)
5 or more positive cervical lymph nodes at presentation
Distant metastatic disease (Stage IVC)
Radiological evidence of gross extracapsular nodal tumor invasion
Anatomy not allowing transoral access and exposure
Prior head and neck cancer at any time (Other than BCC or SCC of skin)
Coexistent second malignancy or history within 5 years of prior malignancy (other than BCC or early SCC skin or curatively treated Stage I carcinoma of cervix)
Peripheral neuropathy >/= grade 1
Have had prior Taxanes or Cisplatin
Concurrent infection
Coexisting medical illness of a severity that might interfere with treatment or follow-up, or who do not have the ability to give informed consent.
Receiving any other investigational agent while on the study