Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
121
Countries
1
Sites
2
oropharyngal cancer
The main objective of this trial is to assess and compare the subjects reported outcomes measurements in term of swallowing (MD Anderson Dysphagia Inventory (MDADI)) 6 months after end of chemoradiotherapy treatment in subjects randomized to either the prophylactic PEG tube group or the reactive PEG tube group.
Key facts
- Sponsor
- Institut Jules Bordet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 11 Dec 2019 → ongoing
- Decision date (initial)
- 2023-08-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Les Amis de l’Institut Jules Bordet
External identifiers
- EU CT number
- 2023-506258-19-00
- EudraCT number
- 2019-001077-87
- ClinicalTrials.gov
- NCT04019548
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety
The main objective of this trial is to assess and compare the subjects reported outcomes measurements in term of swallowing (MD Anderson Dysphagia Inventory (MDADI)) 6 months after end of chemoradiotherapy treatment in subjects randomized to either the prophylactic PEG tube group or the reactive PEG tube group.
Secondary objectives 8
- To assess the Health related QOL (HRQOL) (EORTC QLQ-C30; EORTC QLQ-H&N43 module) and FACT-HN
- To assess CRT related toxicities and PEG tube placement complications
- To assess nutritional status on survival and toxicity outcomes
- To assess the clinical tumour response after study treatment
- To assess the loco regional control (LRC), distant recurrence/distant progression (DR/DP), second primary (SP), disease-free survival (DFS), disease specific survival (DSS), overall survival (OS).
- To assess the impact of HPV and tobacco smoking on these secondary endpoints
- Cost-Effectiveness of each treatment strategy
- Clinical validation of cancer prediction models available at www.predictcancer.org.
Conditions and MedDRA coding
oropharyngal cancer
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Main Trial This is an open-label, multi-centric randomized, phase 3 trial in subjects with advanced oropharyngeal, oral cavity,hypopharyngeal, laryngeal and nasopharyngeal cancer.
The registered subjects will be randomized (1:1) either in the arm with prophylactic PEG tube (pPEG) placement or in the arm with reactive PEG tube (rPEG) placement. Prophylactic PEG tube will be placed before the start of the study treatment (CCRT). The enteral nutrition will start following the assessment by the clinical dietitian in order to complete the current oral consumption according to the estimated energy needs based on 30 to 35 kcal / kg adapted and 1.2 to 1.5 g / proteins/ kg body weight(BW) with an increase as needed during the treatment.
All subjects will be treated with a cisplatin standard chemotherapy regimen and by simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT). Study treatments are described in the section 6.
|
Randomised Controlled | None | pPEG arm: Prophylactic PEG tube will be placed before the start of the study treatment (CCRT). The enteral nutrition will start following the assessment by the clinical dietitian in order to complete the current oral consumption according to the estimated energy needs based on 30 to 35 kcal / kg adapted and 1.2 to 1.5 g / proteins/ kg body weight(BW) with an increase as needed during the treatment. rPEG arm: Reactive PEG tube will be placed and enteral nutrition initiated during the study treatment period in case of: o decrease of oral intake less than 2/3 of estimated energy requirements based on 30-35 kcal / adapted kg BW and 1.2 - 1.5 g/proteins/adapted kg. BW for a period of or anticipated to be, greater than 7 days or o Weight loss ≥ 5% from pre-treatment baseline). |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 19
- Age ≥ 18 years old
- ECOG performance status ≤ 2
- Female and Male
- Newly diagnosed, histologically confirmed primary squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx and nasopharyngeal carcinoma
- Candidate for curative intent radiotherapy and systemic treatment
- No prior or current anticancer treatment for the HNC(e.g. neo-adjuvant chemotherapy, surgery)
- Diagnosis biopsy results available at the time of screening
- HPV/p 16 testing results available at the time of screening for oropharyngeal carcinoma
- Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to the 1st CCRT administration.
- Women of childbearing potential must agree to use of one highly effective method of contraception prior study entry, during the course of the study and at least 6 months after the last administration of cisplatin.
- Men with childbearing potential partner must agree to use condom during the course of this study and for at least 6 months after the last administration of the cisplatin
- Adequate bone marrow function as defined below: - Absolute neutrophil count (ANC) ≥1500/µL or 1.5x109 /L - Hemoglobin ≥ 9 g/dL - Platelets ≥100000/µL or 100x109 /L
- Adequate liver function as defined below: - Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert’s syndrome < 3 x UNL is allowed - AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN - Alkaline phosphatase ≤ 2.5 x ULN
- Adequate renal function as defined below: - Creatinine ≤ 1.5 x UNL and creatinine clearance > 60 mL/min
- Peripheral neuropathy ≤ grade 1
- Hear impaired ≤ grade 1
- Completion of all necessary screening procedures within 15 days prior to randomisation.
- Signed Informed Consent form (ICF) obtained prior to any study related procedure.
- Ability to understand and complete the questionnaires (language proficiency, cognitive functioning) as judged by the principal investigator upon screening)
Exclusion criteria 8
- Severe malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria
- Dysphagia requiring a liquid or puree texture modified diet (grade ≥ 2 (CTCAE_v.5)
- Distant metastasis
- Serious coagulation disorders (INR>1.5, PTT> 50s, platelets <50000/mm3)
- Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator’s opinion, may interfere with completion of the study.
- Other malignancies in the 3 years prior to study entry except of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin
- Pregnant and/or lactating women.
- Known hypersensitivity to the study drug (cisplatin) or excipients.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the global MDADI score at 6 months after end of treatment.
Secondary endpoints 6
- Patient reported outcomes via self-administered questionnaires: HRQOL (EORTC QLQ–C30 and EORTC QLQ-H&N43 module) and FACT-HN, Oral-Oropharyngeal toxicity according to the oral mucositis weekly questionnaire: Head and Neck cancer (OMWQ-NH) completed by the subject, Salivary toxicity according to the xerostomia questionnaire completed by the subject
- Incidence, type and severity of all adverse events (AEs) and serious adverse events according to CTCAE version 5.0
- Incidence, type and severity of radiotherapy related AEs also according to Radiation Therapy Oncology Group (RTOG) / European Organisation for Research and treatment of Cancer (EORTC) scores
- Impact of nutritional status on survival and toxicity outcomes by using, GLIM criteria (Global Leadership Initiative on Malnutrition) criteria and CRP, albumin and pre-albumin
- Tumour response after study treatment measured at 3 months by DECT and PET-CT after end of treatment
- End of treatment. Subject outcome: loco regional control (LRC), distant recurrence/distant progression (DR/DP), second primary (SP), disease-free survival (DFS), disease specific survival (DSS), overall survival (OS)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB07483MIG · Substance
- Active substance
- Cisplatin
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 100 mg/m2 milligram(s)/sq. meter
- Max total dose
- 200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 3
SUB12988MIG · Substance
- Active substance
- Barium Sulfate
- Pharmaceutical form
- ORAL SUSPENSION
- Route of administration
- ORAL USE
- Max daily dose
- 50 mg/ml milligram(s)/millilitre
- Max total dose
- 250 mg/ml milligram(s)/millilitre
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08234MIG · Substance
- Active substance
- Iomeprol
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg/ml milligram(s)/millilitre
- Max total dose
- 1200 mg/ml milligram(s)/millilitre
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07680MIG · Substance
- Active substance
- Fludeoxyglucose (18F)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 MBq megabecquerel(s)
- Max total dose
- 00 MBq megabecquerel(s)
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Institut Jules Bordet
- Sponsor organisation
- Institut Jules Bordet
- Address
- Mijlenmeersstraat 90
- City
- Brussels
- Postcode
- 1070
- Country
- Belgium
Scientific contact point
- Organisation
- Institut Jules Bordet
- Contact name
- CTSU
Public contact point
- Organisation
- Institut Jules Bordet
- Contact name
- CTSU
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 121 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2019-12-11 | 2019-12-11 | 2025-10-08 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-506258-19-00_Redacted | 4.0 |
| Protocol (for publication) | D4_Patient_Diary_FR | 1 |
| Protocol (for publication) | D4_Patient_Diary_NL | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment_arragement | 1.0 |
| Subject information and informed consent form (for publication) | L1_ICF_Adults_FR_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_ICF_Adults_NL_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_Addendum_A_FR | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_Addendum_A_NL | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_summary_changes | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Cisplatin | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol_Synopsis_BE_DE_2023-506258-19-00 | 4.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_Synopsis_BE_NL_2023-506258-19-00 | 4.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_Synopsis_FR_2023-506258-19-00 | 4.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-12 | Belgium | Acceptable 2023-07-03
|
2023-08-02 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-26 | Belgium | Acceptable 2025-02-17
|
2025-02-17 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-04-24 | Belgium | Acceptable 2025-05-26
|
2025-05-28 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-10-06 | Belgium | Acceptable 2025-05-26
|
2025-10-06 |