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Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma (QoLATI)

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ClinicalTrials.gov Identifier: NCT04124198
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : October 11, 2019
Sponsor:
Collaborators:
Naestved Hospital
Herlev Hospital
Aarhus University Hospital
Odense University Hospital
Information provided by (Responsible Party):
Christian von Buchwald, Rigshospitalet, Denmark

Brief Summary:

Oropharyngeal squamous cell carcinoma (OPSCC) is now the most frequently diagnosed head and neck cancer in Denmark which is mainly due to the increase of Human Papillomavirus (HPV). Patients with HPV-positive OPSCC have a significantly higher survival rate compared to HPV-negative OPSCC. The traditional primary treatment modality in Denmark is Intensity Modulated Radiation Therapy (IMRT), and in advanced stages in combination with chemotherapy. Since 2009, Transoral Robotic Surgery (TORS) has enabled surgeons to perform minimally invasive surgery as an alternative to standard radiotherapy treatment which is considered the primary treatment for OPSCC in many countries. There is a lack of randomised trials comparing long-term functional outcomes after TORS or IMRT. Current data are mostly derived from retrospective studies with selection bias. However, several small retrospective studies have shown promising results when comparing the two treatment modalities in favour of TORS with regards to treatment related swallowing function and quality of life (QoL) without compromising survival outcomes.

This study aims to evaluate the early and long-term functional outcomes following two treatment arms 1) TORS combined with neck dissection and 2) IMRT±concurrent chemotherapy with a special focus on swallowing-related QoL.


Condition or disease Intervention/treatment Phase
Oropharynx Cancer Oropharynx Squamous Cell Carcinoma Carcinoma, Squamous Cell Carcinoma Oropharyngeal Neoplasms Neoplasms, Squamous Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Pharyngeal Neoplasms Malignant and Unspecified Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Neoplasms by Site Otorhinolaryngologic Diseases Pharyngeal Diseases Papillomavirus Infections Virus Diseases DNA Virus Infections Tumor Virus Infections Quality of Life Radiation: Intensity-Modulated Radiation Therapy (IMRT) Drug: Cisplatin Drug: Nimorazole. Procedure: Transoral Robotic Surgery (TORS) with neck dissection Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Quality of Life After Primary Transoral Robotic Surgery vs Intensity-modulated Radiotherapy for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma: A Randomized National Trial
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2029

Arm Intervention/treatment
Experimental: Transoral robotic surgery (TORS) Procedure: Transoral Robotic Surgery (TORS) with neck dissection
Robotic-assisted resection of the primary oropharyngeal tumour and ipsilateral selected neck dissection of lymph node levels II-IV. Patients with a primary base of tongue cancer or with significant involvement of tongue base or the soft palate defined as above 1 cm, will be offered a bilateral neck dissection of levels II-IV.

Active Comparator: Intensity-Modulated Radiation Therapy (IMRT)

Patients with clinical T1N0 stage are offered accelerated radiotherapy to 66 Gy/33fractions with concurrent nimorazole.

Patients with clinical T2N0 stage are offered either accelerated radiotherapy to 66 Gy/33fractions with the option of weekly cisplatin to fit patients or hyper-fractionated accelerated radiotherapy to 76 Gy/56fractions both with concurrent nimorazole.

Patients with clinical T1-T2, N1 stage are offered accelerated radiotherapy to 66 Gy/33 fractions and nimorazole with the addition of concurrent weekly cisplatin 40 mg/sqm to fit patients.

Radiation: Intensity-Modulated Radiation Therapy (IMRT)
Accelerated or hyper-fractionated radiotherapy

Drug: Cisplatin
Concurrent weekly cisplatin 40 mg/sqm to fit patients

Drug: Nimorazole.
Concurrent nimorazole




Primary Outcome Measures :
  1. Swallowing related quality of life by MDADI [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Difference in swallowing related quality of life measured by a composite MD Anderson Dysphagia Inventory (MDADI) score. The MDADI is a 20-item self-administered questionnaire that quantifies swallowing-related quality of life. Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. Summary and subscale MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).


Secondary Outcome Measures :
  1. Nasogastric or percutaneus tube dependency [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Tube dependency defined as number of days/weeks/months with tube inserted

  2. Swallowing function by fiberendoscopic evaluation [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Fiberendoscopic Evaluation of Swallowing (FEES) is rated by following scales: a 8-point Penetration-Aspiration Scale (PAS) where a score of 1 reflects no entry of material into the airway, scores of 2-5 reflect penetration of material past the laryngeal additus into the supraglottic space and traveling as far as the true vocal folds, while scores of 6-8 reflect tracheal aspiration of material below the true vocal folds; Yale Pharyngeal Residue Severity Rating Scale: image-based assessment of post-swallow pharyngeal residue severity as observed during swallowing. Five-point ordinal rating scale based on residue location (vallecula and pyriform sinus) and amount (none, trace, mild, moderate, and severe); the summary DIGEST grading: grade 1= mild, grade 2= moderate, grade 3= severe, and grade 4= life threatening pharyngeal dysphagia.

  3. Swallowing function by modified barium swallowing [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Modified Barium Swallowing (MBS) is a fluoroscopic procedure designed to determine whether food or liquid is aspirated. Following scales are used to assess MBS: a 8-point Penetration-Aspiration Scale (PAS): a score of 1 reflects no entry of material into the airway, scores of 2-5 reflect penetration of material past the laryngeal additus into the supraglottic space and traveling as far as the true vocal folds, while scores of 6-8 reflect tracheal aspiration of material below the true vocal folds; the summary DIGEST grading: grade 1= mild, grade 2= moderate, grade 3= severe, and grade 4= life threatening pharyngeal dysphagia.

  4. Patient reported quality of life by EORTC-QLQ-H&N35 [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC-QLQ-H&N35. The head and neck-specific module EORTC QLQ-H&N35 contains 35 items, which can be condensed into 7 multi-item and 11 single-item scales. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

  5. Patient reported quality of life by EORTC QLQ-C30 [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

  6. Treatment-related pain [ Time Frame: evaluated at baseline up to 12 months after treatment ]
    Daily (experimental arm) or weekly (control arm) self-reported visual analogue scale (VAS) score from 0-10 points in which a higher score indicates greater pain intensity. Measured until no treatment-related pain is recorded by the patient and with no need of treatment-related pain medication

  7. Weight [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
  8. Patients returning to work after treatment [ Time Frame: evaluated at baseline, 3 and 12 months after treatment ]
    Defined as the time (number of days) before returning to work or failure to do so after treatment.

  9. Morbidity after staging neck after staging neck dissection [ Time Frame: evaluated from time of neck dissection up to 14 days after treatment ]
    Monitoring of events of bleeding, lymphedema or impaired nerve function after staging neck dissection

  10. Nerve function [ Time Frame: evaluated at baseline and up to 12 months after treatment ]
    Evaluation of nerve function at risk during surgery (spinal accessory, hypoglossal, marginal mandibular branch of the facial nerve, lingual and vagal nerve) will be assessed by a clinical examination based on the innervation and function of each nerve during follow-up after surgery. Nerve function is determined as dichotomous variable: functioning/not-functioning.

  11. Late toxicity [ Time Frame: evaluated at 3, 6, 12, 24, 36, 48 and 60 months after treatment ]
    Using The Radiation Therapy Oncology Group/The European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Score. Uses a grading system from 0-5 for different tissue organs: 0 - no symptoms, 5 - death directly related to radiation effects

  12. Overall survival [ Time Frame: evaluated from time of randomization up to 5 years ]
    Time from randomization to death from any cause.

  13. Disease-free survival [ Time Frame: evaluated from time of randomization up to 5 years ]
    Time from randomization to sign of cancer is found.

  14. Disease-specific survival [ Time Frame: evaluated from time of randomization up to 5 years ]
    Time from randomization to death from the disease (oropharyngeal cancer).

  15. Distant recurrence [ Time Frame: evaluated from time of randomization up to 5 years ]
    Time from randomization to distant recurrence

  16. Loco-regional recurrence [ Time Frame: evaluated from time of randomization up to 5 years ]
    Time from randomization to recurrence in same T-site or N-site as initial cancer localization



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years or older
  2. Able to provide informed consent
  3. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2
  4. Histologically confirmed oropharyngeal squamous cell carcinoma (exclusively palatine tonsils and base of tongue tumours) with known p16 status
  5. Clinical tumour stage cT1-2 according to The Union for International Cancer Control (UICC), tumor (T), nodes (N), and metastases (M), (TNM) classification, 8th edition.
  6. Clinical nodal stage cN0-1 according to UICC, TNM classification, 8th edition, however in p16 positive patients with unilateral metastasis, only a nodal metastasis up to a maximum of 3 cm in greatest diameter according to pre-operative imaging will be included.
  7. Diagnostic imaging including computed tomography/magnetic resonance imaging (CT/MRI) performed within 14 days at time of randomization.
  8. A tumour that is considered resectable according to MRI, clinical examination and/or ultrasound

Exclusion Criteria:

  1. Serious medical comorbidities or ECOG/WHO performance status >2. Other contraindications to radiotherapy, chemotherapy or surgery
  2. Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic
  3. Distant metastasis
  4. Clinically and radiologic signs of nodal extracapsular extension
  5. Previous radiotherapy of the head and neck
  6. Previous head and neck cancer
  7. Significant trismus (maximum inter-incisal opening ≤ 35mm) [46]
  8. Unable or unwilling to complete quality of life questionnaires
  9. Posterior pharyngeal wall involvement
  10. Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124198


Contacts
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Contact: Hani Ibrahim Channir, MD, PhD +4520259637 Hani.ibrahim.channir.02@regionh.dk

Locations
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Denmark
Aarhus University Hospital Not yet recruiting
Aarhus, Denmark
Contact: Thomas Kjærgaard, MD, PhD         
Principal Investigator: Thomas Kjærgaard, MD, PhD         
Sub-Investigator: Pernille Lassen, MD, PhD         
Copenhagen University Hospital Rigshospitalet Recruiting
Copenhagen, Denmark
Contact: Hani Ibrahim Channir, MD, PhD       Hani.Ibrahim.Channir.02@regionh.dk   
Principal Investigator: Niclas Rubek, MD         
Sub-Investigator: Jeppe Friborg, MD, PhD         
Odense University Hospital Not yet recruiting
Odense, Denmark
Contact: Christian Godballe, MD, PhD         
Principal Investigator: Christian Godballe, MD, PhD         
Sub-Investigator: Jørgen Johansen, MD         
Sponsors and Collaborators
Christian von Buchwald
Naestved Hospital
Herlev Hospital
Aarhus University Hospital
Odense University Hospital
Investigators
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Study Chair: Christian von Buchwald, MD, DMSc. Department of Otorhinolaryngology, Head and Neck Surgery, Copenhagen University Hospital Rigshospitalet
Principal Investigator: Niclas Rubek, MD Department of Otorhinolaryngology, Head and Neck Surgery, Copenhagen University Hospital Rigshospitalet

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Responsible Party: Christian von Buchwald, Clinical Professor and Study Chair, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT04124198     History of Changes
Other Study ID Numbers: The QoLATI Study
DAHANCA 34 ( Other Identifier: The Danish Head and Neck Cancer Group )
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Christian von Buchwald, Rigshospitalet, Denmark:
Oropharyngeal squamous cell carcinoma T1-T2, N0-1
Transoral robotic surgery
Intensity Modulated Radiation Therapy
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Papillomavirus Infections
DNA Virus Infections
Tumor Virus Infections
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Oropharyngeal Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Neoplasms
Virus Diseases
Otorhinolaryngologic Diseases
Stomatognathic Diseases
Nimorazole
Cisplatin
Antineoplastic Agents
Antitrichomonal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents