Study Comparing Fibula Free-flap MR With or Without PVP in Patients With OOPC

Oral Cavity Squamous Cell Carcinoma Clinical Trial

— CURVE  

Official title:

A Randomized Prospective Multicenter Study Comparing Fibula Free-flap Mandibular Reconstruction With or Without Preoperative Virtual Planning in Patients With Oral or Oropharyngeal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04725396
• Other study ID #: UC-HNG-2009
• Secondary ID: 2020-A02655-34
• Status: Recruiting
• Phase: N/A
• Start date: April 20, 2021
• Est. completion date: December 1, 2024

Study information

• Verified date: June 2024
• Source: UNICANCER
• Contact: Michaël CHEVROT, Ph.D
• Phone: +33171936161
• Email: m-chevrot[@]unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a national multicenter, randomized, stratified, open label study, aiming to compare mandibular reconstruction (MR) with or without preoperative virtual planning (PVP), in patients with oral/oropharyngeal cancer (OOPC).

Description:

PVP-assisted MR includes the production of the surgical cutting guides required for mandibular resection and fibula free-flap conformation and of the preformed plates for flap osteosynthesis (for all patients, PVP will be done by the same laboratory: Materialise laboratory).

PVP-assisted MR includes the production of :

• surgical cutting guides required for mandibular resection and fibula free-flap conformation

• preformed plates for flap osteosynthesis

Patients will be selected after the multidisciplinary decision of oncological surgery including segmental mandibulectomy and immediate MR. Patients will be randomized in 2 groups (ratio 1:1, stratified on center and tumor N status [0-1 vs 2-3]).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Aged 18 years or over

2. Primary or recurrent OOPC, histologically proven, requiring segmental mandibulectomy

3. Planned immediate fibula free flap MR to be performed at the same time as the tumor ablation by segmental mandibulectomy

4. MR requiring at least one osteotomy for contouring the flap (i.e. at least 2 bone fragments)

5. East Cooperative Oncology Group (ECOG) performance status 0 or 1

6. American Society of Anesthesiologists Physical Status (ASA) score 1, 2, or 3

7. Patients considered fit for surgery as decided by the multidisciplinary team

8. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures

9. Patients must be affiliated to a Social Security System (or equivalent)

10. Patients must have signed a written informed consent form prior to any trial specific procedures. If the patients are physically unable to give their written consent, a trusted person of their choice, not related to the investigator or the sponsor, can confirm in writing the patient's consent

Exclusion Criteria:

1. Non resectable tumors (T4b primary tumor, non resectable metastatic lymph nodes)

2. Comorbidities factors that would contraindicate surgery (such as severe peripheral artery disease)

3. MR requiring no osteotomy for contouring the flap (i.e. one bone fragment)

4. Patients with distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g. CT thorax and upper abdomen or positron emission tomography (PET)-CT

5. Other uncontrolled malignancy

6. Serious, non-healing or dehiscing wound, active ulcer or ongoing bone fracture at the free-flap donor site

7. Patients unwilling or unable to comply with the medical follow-up required by the trial because of psychosocial, familial, social, or geographical reasons

8. Participation in another clinical study with an investigational medicinal product during the last 30 days prior to inclusion

9. Patients deprived of their liberty or under protective custody or guardianship

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oral Cavity Squamous Cell Carcinoma
• Oropharynx Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Device:
• Mandibular Reconstruction (MR) with Preoperative Virtual Planning (PVP).
PVP-assisted mandibular reconstruction includes the production of the surgical cutting guides required for mandibular resection and fibula free-flap conformation and of the preformed plates for flap osteosynthesis (for all patients, PVP will be done by the same laboratory).
• Conventional Mandibular Reconstruction (MR without PVP)
Conventional Mandibular Reconstruction

Locations

Country	Name	City	State
France	CHU Groupe Hospitalier Pellegrin	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Oscar Lambret	Lille
France	CHU Gui de Chauliac	Montpellier
France	CHU Hotel Dieu	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHU Pontchaillou	Rennes
France	IUCT-O	Toulouse
France	CHR de Valenciennes	Valenciennes
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	General Oral Health Assessment Index (GOHAI)	Oral health-related quality of life (QoL) measured 1 year after surgery using the GOHAI in the 2 groups of patients (MR with or without PVP).; The GOHAI is an oral-disease-specific QoL measure made by the patient. The GOHAI comprises 12 items grouped into three dimensions: the functional dimension (eating, speaking, swallowing); the pain or discomfort dimension (drugs, gingival sensitivity, discomfort when chewing certain foods); and, the psychosocial dimension (concerns, relational discomfort, appearance). The response format for each item is based on a five-point Likert scale: always = 1; often = 2; sometimes = 3; seldom = 4; never = 5. A summary score (ranging from 0 to 60) is calculated for each patient with a higher score indicating better oral health. GOHAI scores close to 30 have been reported in head and neck cancer patients after oncologic surgery and pedicled or free flap reconstruction.	1-year
Secondary	Time between randomization and surgery	Mean and median time between randomization and surgery	At the time of surgery, up to 45 days after randomization
Secondary	Total operative time and flap ischemia time	Mean and median total operative time and mean and median flap ischemia time	Post surgery, up to 45 days after randomization
Secondary	Postoperative surgical complication rate (including free-flap failure rate)	Surgical complication rates defined as local complication requiring another intervention in the first postoperative month, including free-flap failure rates	Post surgery, up to 45 days after randomization
Secondary	Delayed surgical complication rate	Delayed surgical complication rates defined as local complication occurring after the first postoperative month: non-union (pseudo-arthrosis), osteosynthesis-associated infection…	Post surgery, up to 45 days after randomization
Secondary	Functional outcome: Performance Status Scales for Head and Neck (PSS-HN)	The PSS-HN is a 3-item scale designed to evaluate functional performance of H&N cancer patients, specifically Normalcy of Diet, Eating in Public, and Understandability of Speech. Each subscale is rated based on semi-structured interview with a score of 0 to 100, with higher scores indicating better performance. The subscale scores are reported separately, and the Normalcy of Diet subscale will be the primary score of interest for this trial.; The PSS-HN can be rated by health professionals including speech & language therapists and research nurses. The person collecting this data will remain consistent, as far as is feasible, throughout the course of the study. Scores are determined following an unstructured interview.	At baseline and at 1 year
Secondary	Functional outcome: Mouth opening range/capacity	Functional outcomes assessed by mouth opening range/capacity at baseline and at 1 year.; It will be performed by using a caliper square to measure in millimeters the inter-incisor gap, assessed by the investigator.	At baseline and at 1 year
Secondary	Functional outcome: MD Anderson Dysphagia Inventory (MDADI)	The MDADI is a self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QoL of patients with head and neck cancer. It surveys QoL issues relevant to swallowing via several subscales: Emotional, Functional, and Physical. A fourth measurement, the Global subscale, is a single question designed to establish quickly an overall assessment that pertains to swallowing. A score ranging from 0 to 100 is calculated for each subscale, with higher scores indicating higher levels of dysphagia.	1 year
Secondary	Functional outcome: Speech Handicap Index (SHI)	The SHI is a well-validated and widely used self-questionnaire for assessing speech problems in OOPC patients. It comprises 3 items and provides insight into the nature and severity of patients' complaints. Response categories for all but 1 item range on a 5-point scale (''never,'' ''almost never,'' ''sometimes,'' ''almost always,'' and ''always''). The questionnaire also includes an overall speech quality item, with 4 response categories (''good,'' ''reasonable,'' ''poor,'' and ''severe''). A total SHI score is calculated by summing all items (score range, 0-120), with higher scores indicating higher levels of speech related problems.	1 year
Secondary	Functional dental status	Functional dental status (>6; 4-6, <4 functional dental units; type of dental rehabilitation) of the patients	At baseline and at 1 year
Secondary	Aesthetic outcome	Subjective assessment of the aesthetic outcome in the head and neck area using a visual analog scale (VAS) by the patient and the surgeon (assessed separately).; The AESTHETIC VAS is a validated, subjective measure for esthetical perception. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "very poor looking"(0) and "very nice looking" (10).	1 year
Secondary	Morphological results: mandibular angle	Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The mandibular angle (in degrees) measured the amplitude of the angle existing between the ramus and body of the mandible.	At 1 year
Secondary	Morphological results: bi-gonial diameter	Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The bi-gonial diameter (in millimeter), a measure of the contracture/reduction of the arch, is intended to measure the preservation of the native mandibular arch anatomy.	At 1 year
Secondary	Morphological results: position of the gnathion	Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The lateral deviation (in millimeter) of gnathion in relation to the midsagittal plane will determined the degree of mandibular asymmetry.	At 1 year
Secondary	Pain in the head and neck area	"no pain" (0) and "worst pain" (10).	At 1 year
Secondary	Evolution of patient QoL: GOHAI score	Evolution of patient QoL GOHAI score at 6 months (this score will be compared to the score measured at baseline and at 1 year).; The GOHAI is an oral-disease-specific QoL measure made by the patient. The GOHAI comprises 12 items grouped into three dimensions: the functional dimension (eating, speaking, swallowing); the pain or discomfort dimension (drugs, gingival sensitivity, discomfort when chewing certain foods); and, the psychosocial dimension (concerns, relational discomfort, appearance). The response format for each item is based on a five-point Likert scale: always = 1; often = 2; sometimes = 3; seldom = 4; never = 5. A summary score (ranging from 0 to 60) is calculated for each patient with a higher score indicating better oral health. GOHAI scores close to 30 have been reported in head and neck cancer patients after oncologic surgery and pedicled or free flap reconstruction.	At baseline, at 6 months, and at 1 year
Secondary	Evolution of patient QoL: Quality of life questionnaire - Core 30 (QLQ-C30) score	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.; The EORTC QLQ-C30 is a general self-report questionnaire designed to assess QoL in cancer patients. It consists of five functioning scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea, and vomiting), a global QoL scale, and six single questions assessing additional symptoms commonly reported by cancer patients.; As recommended by the EORTC, the scales and single-item variables of the QLQ-C30 will be linearly transformed into a score from 0 to 100. A high score for a functioning scale and for the global QOL scale represents a better level of functioning, whereas a high score for a symptom scale or a single item scale denotes a high level of symptoms or problems.	At baseline, at 6 months and at 1 year.
Secondary	Evolution of patient QoL: Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35) score	The EORTC QLQ-H&N35 is a tumor specific self-report questionnaire for head and neck cancer patients including seven symptoms scales (pain, swallowing, senses, speech, social eating, social contacts, and sexuality) and six single items (teeth problems, mouth opening, dry mouth, sticky saliva, coughing, and feeling ill).; As recommended by the EORTC, the scales and single-item variables of the H&N35 questionnaire will be linearly transformed into a score from 0 to 100. A high score for a functioning scale and for the global QOL scale represents a better level of functioning, whereas a high score for a symptom scale or a single item scale denotes a high level of symptoms or problems.	At baseline, at 6 months and at 1 year.