Comparison of an Initial Active Follow-up and Therapeutic Care on Functional Outcome and Quality of Life in Patients With Head and Neck Paragangliomas

N/ANot Yet RecruitingNCT07784595

Hospices Civils de Lyon122 enrolled

Overview

Head and neck paragangliomas (HNPGs) are predominantly non-secreting, benign and slow-growing tumors. Although most patients remain asymptomatic, up to 30% develop symptoms related to local tumor growth and fewer than 5-10% develop metastatic disease. Surgery has long been considered the standard treatment, while radiotherapy and active surveillance represent alternative management strategies. Treatment-related morbidity and impaired quality of life have been reported in patients with HNPGs; however, the impact of immediate intervention compared with an initial active surveillance strategy has not been prospectively evaluated. This multicenter randomized controlled trial aims to compare active surveillance with immediate intervention in patients with newly diagnosed carotid or vagal paragangliomas. The study hypothesis is that an initial active surveillance strategy increases the time before functional outcome deterioration, particularly ENT-related symptoms, while not resulting in a higher complication rate when treatment is subsequently performed. Eligible patients will undergo baseline assessment including a specialized ENT examination to evaluate cranial nerve function and cervical MRI (or contrast-enhanced CT when MRI is contraindicated) to confirm tumor location, size, and the absence of lymphadenopathy or atypical imaging features. After providing written informed consent, participants will be centrally randomized in a 1:1 ratio, stratified by study center and tumor location, to either active surveillance or immediate intervention. Patients assigned to active surveillance will undergo regular clinical and radiological follow-up, with treatment initiated only if disease progression or symptom development warrants intervention. Patients assigned to immediate intervention will receive surgery or radiotherapy according to multidisciplinary team recommendations and local practice, within six months after randomization. Patients who decline participation in the randomized trial, as well as those who are not eligible for randomization, may be offered participation in a parallel observational study collecting clinical, imaging, treatment and outcome data according to routine practice. Patient quality of life will also be assessed throughout the study (experimental and observational) using validated questionnaires.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

Active follow-upOTHER

Patients will not receive any treatment, they will undergo annual follow-up assessments according to the standard of care. Upon disease progression, patients will be allowed to switch to the treatment group.

SurgeryPROCEDURE

Patients may be treated with surgery to remove the paraganglioma within 6 months after randomization.

RadiationRADIATION

Patients may be treated with radiation within 6 months after randomization.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients ≥ 18 years-old, * Diagnosis of carotid or vagal HNPG with a largest diameter more than 10 mm * Diagnosis confirmed by imaging reading (MRI of CT scan) from less than 6 months, * Study eligibility validated in multidisciplinary discussion, * Patient followed in the reference center, * Preliminary written informed consent before any study-specific intervention Exclusion Criteria: * Patient with initial nerve palsy due to the evaluated HNPG, * Patient with non-typical presentation suggestive of aggressiveness (tumor pain, atypical imaging, suspicious lymphadenopathy), * Malignant HNPG identified by extra cervical lesion on metabolic imaging, * More than one HNPG at inclusion * Secreting HNPG defined as plasma or urine metanephrine or normetanephrine more than 2 times ULN, * Patient already treated with cervical radiotherapy, * Patient already treated with systemic therapy for another pheochromocytoma or paraganglioma, * Patient with another evolutive disease or other condition resulting on a life expectancy of less than 5 years at the investigator's discretion, * Patient unable or unwilling to be treated at the study center * Patients currently enrolled in another interventional study including investigational medicinal products or device, * Female patients who are pregnant, lactating or women of child-bearing potential without highly effective methods of contraception * Persons deprived of their liberty by a judicial or administrative decision * Persons under psychiatric care * Persons admitted to a health or social institution for purposes other than research * Adults subject to a legal protection measure (guardianship, curatorship) * Persons not affiliated to a social security scheme or beneficiaries of a similar scheme

Locations (8)

Fédération d'endocrinologie, Hôpital cardiologique - Groupement Hospitalier Est - Hospices Civils de Lyon

Bron, France

Service ORL - Hôpital Lariboisière - AP-HP

Paris, France

Médecine Nucléaire - Hôpital Pitié-Salpêtrière - AP-HP

Paris, France

Service d'Endocrinologie - Hôpital Cochin

Paris, France

Service Endocrinologie et métabolismes - Hôpital Européen Georges Pompidou - AP-HP

Paris, France

Service d'endocrinologie, diabétologie et nutrition - Hôpital Haut-Lévêque - CHU de Bordeaux

Pessac, France

Service Endocrinologie Diabétologie Nutrition - Hôpital Nord Laennec - CHU de Nantes

Saint-Herblain, France

Endocrinologie, diabète et nutrition - Hôpital de Hautepierre - CHRU de Strasbourg

Strasbourg, France

Outcomes

Primary Outcomes

Time to functional outcome deterioration

Time to functional outcome deterioration is defined as the delay between inclusion and functional outcome deterioration. Patients without functional deterioration are censored at their last functional assessment. Functional outcome deterioration is defined as a decrease in at least 12 points (or 8.6%) of the FACT H\&N score since inclusion. The FACT-H\&N score ranges from 0 to 148. The higher the score, the better the quality of life.

Time frame: From baseline to 5 years maximum

Secondary Outcomes

Evolution of the functional outcomes between the groups

Functional outcomes are defined by the overall score of the FACT H\&N in both groups. The FACT-H\&N score ranges from 0 to 148. The higher the score, the better the quality of life.

Time frame: Baseline, 1 year and 5 years

Evolution of the functional outcomes between the groups

Functional outcomes are defined by the overall score of the EORTC QLQ-HN43 in both groups. The scores of the EORTC QLQ-HN43 module are standardized on a scale from 0 to 100. For all symptom scales, a higher score reflects greater symptom burden and poorer quality of life.

Time frame: Baseline, 1 year and 5 years

Quality of life (QoL)

Change on QoL in both groups assessed by the global health status score of the EORTC QLQ-C30. The scores of the EORTC QLQ-C30 questionnaire are standardized on a scale from 0 to 100. A higher score reflects a better level of functioning and a better quality of life.

Time frame: Baseline, 1 year and 5 years

Anxiety

Change on the anxiety evaluation in both groups assessed by HAD scale. The higher the score, the greater the severity of anxiety or depressive symptoms. The total score ranges from 0 to 42.

Time frame: Baseline, 1 year and 5 years

Factors associated with a significant quality of life

Variation of at least 10% of the global health status score of the EORTC QLQ-C30. The scores of the EORTC QLQ-C30 questionnaire are standardized on a scale from 0 to 100. A higher score reflects a better level of functioning and a better quality of life.

Time frame: Baseline, 1 year, 5 years

Factors associated with functional outcomes

Variation of at least 10% of the one of the scales of the QLQ-HN43. The scores of the EORTC QLQ-HN43 module are standardized on a scale from 0 to 100. For all symptom scales, a higher score reflects greater symptom burden and poorer quality of life.

Time frame: Baseline, 1 year, 5 years

Factors associated with anxiety deterioration

Variation of at least 10% of the anxiety scale of HAD. The Hospital Anxiety and Depression Scale (HADS) consists of two subscales including anxiety. Each subscale ranges from 0 to 21, with higher scores reflecting more severe symptomatology.

Time frame: Baseline, 1 year, 5 years

Switch proportion, reason and time to therapeutic intervention

Proportion of patients in the active FU group needing later therapeutic intervention, the reason and the time to therapeutic intervention

Time frame: From baseline to study end

Progression/recurrence rate

Time to progression/recurrence defined as the delay between inclusion and tumor progression in all groups (20% increase in one diameter increase according to RECIST 1.1 criteria, spread metastasis or tumor appearance after total removal). Patients without progression/recurrence will be censored at the last imaging assessment. At least, one assessment will be conducted at 5 years.

Time frame: From baseline to study end

Surgery complication rate

Proportion of all operated patients with complications post-surgery (Clavien-Dindo classification).

Time frame: At 1 year and 5 years

Radiation therapy complication rate

Proportion of all irradiated patients with complications post irradiation (CTCAE V5.0)

Time frame: At 1 year and 5 years

Disease progression

Characterization of spontaneous tumor evolution in patients with active FU

Time frame: At 1 year and 5 years

Proportion of distant metastasis

Characterization of spontaneous tumor evolution in patients with active FU

Time frame: At 5 years

Comparison of an Initial Active Follow-up and Therapeutic Care on Functional Outcome and Quality of Life in Patients With Head and Neck Paragangliomas

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts