A clinical trial in patients with head and neck cancer of Debio 1143 in combination with platinum-based chemotherapy and radiotherapy
- Conditions
- ocally advanced squamous cell carcinoma of the head and neck (SCCHN)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000377-25-IT
- Lead Sponsor
- DEBIOPHARM INTERNATIONAL S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 700
1. Willing and able to sign written informed consent prior to study screening.
2. Male or female >= 18 years of age (or based on the country legal age limit for adults) on day of signing the ICF.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
4. Histologically confirmed diagnosis in previously untreated LA-SCCHN patient (stage III, IVA or IVB according to the American Joint
Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) suitable for definitive CRT as defined in the protocol.
5. Evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan (CT-scan) or magnetic
resonance imaging (MRI), based on RECIST v 1.1.
6. For OPC patients, primary tumors must be HPV-negative as determined by p16 expression using immunohistochemistry (IHC).
7. Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy or jejunostomy placed.
8. No hearing loss by clinical assessment.
9. Peripheral neuropathy < grade 2
10. Adequate hematologic, renal and hepatic function as defined in the protocol.
11. Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must have a negative serum
pregnancy test at screening and must not be breastfeeding. Nonsterilized males who are sexually active with a female partner of
childbearing potential must agree to use adequate birth control as defined in the protocol from ICF signature to 6 months after the last
administration of chemotherapy or 3 months after the last dose of Debio 1143/matched placebo, whichever is the latest.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Primary tumor of nasopharyngeal, paranasal sinuses, nasal or oral cavity, salivary, thyroid or parathyroid gland pathologies, skin or
unknown primary site.
2. Metastatic disease (stage IVC as per AJCC/TNM, 8th Ed.).
3. Prior definitive or adjuvant RT and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or
any other prior SCCHN systemic treatment, including investigational agents.
4. Use within 14 days prior to randomization or requirement for ongoing treatment with any drug(s) on the prohibited medication list.
5. Treatment with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment.
6. Known history of infection with HIV. If unknown history of HIV, an HIV screening test is to be performed and subjects with positive
serology for HIV-1/2 must be excluded.
7. Known chronically active HBV or HCV infection. If unknown status, see further details in the protocol.
8. Other infections (viral and/or bacterial and/or mycotic) requiring systemic treatment.
9. Live-attenuated vaccinations within 30 days prior to first investigational treatment administration.
10. Ongoing uncontrolled infection requiring intravenous antibiotic therapy within 1 week prior to randomization.
11. Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery that may
limit oral absorption.
12. Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional
support), OR plasmatic albumin <3.0 g/dL.
13. Active gastrointestinal bleeding, or any other uncontrolled bleeding requiring more than 2 red blood cell transfusions or 4 units of packed
red blood cells within 4 weeks prior to randomization.
14. Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe
extensive psoriasis) requiring ongoing treatment with anti-TNF medication.
15. Any concomitant medication known to prolong the QT interval that cannot be discontinued or replaced by safe alternative medication within
7 days prior to start of treatment.
16. Impaired cardiovascular function or clinically significant cardiovascular diseases, see further details in the protocol.
17. Symptomatic pulmonary disease requiring continuous or intermittent oxygen supply.
18. History of another malignancy within the last 3 years prior to randomization, with the exception of completely resected non-melanoma
cell skin cancer outside the head and neck area or completely resected stage I breast cancer, or completely resected in-situ non-muscular
invasive bladder, cervix and/or uterine carcinomas.
19. Known contraindication to undergoing positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG-PET) scans,
contrast-enhanced MRI or contrast-enhanced CT scans.
20. Known allergy to Debio 1143, cisplatin or any excipient known to be present in Debio1143 or in the placebo formulation.
21. Non-compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C).
22. Any ongoing condition or disorder, before randomization, including drug(s) or alcohol abuse, which in the judgment of the Investigator
would make the patient inappropriate for entry into the study or precluding his/her ability to comply with study procedures.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate superior efficacy of Debio 1143 vs placebo when added to CRT in locally advanced SCCHN.;Secondary Objective: - To assess the efficacy of Debio 1143 compared to placebo when added to CRT according to additional efficacy endpoints.<br>- To compare safety, tolerability and treatment compliance of Debio 1143 vs placebo, when added to CRT.<br>- To compare the health-related quality of life of Debio 1143 vs placebo when added to CRT using patient-reported outcome questionnaires.;Primary end point(s): Event- Free Survival (EFS) as defined in the protocol.;Timepoint(s) of evaluation of this end point: Endpoints will be evaluated in the timepoints listed in the protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Progression-Free Survival (PFS) or death from any cause.<br>- Locoregional control as defined in the protocol.<br>- Objective response rate.<br>- CR rate.<br>- Duration of response as defined in the protocol.<br>- Overall survival.<br>- Proportion of subjects with radical salvage surgery.<br>- Time to subsequent systemic cancer treatments.<br>- Incidence and severity of adverse events, serious adverse events and adverse events of special interest, changes in laboratory values, vital signs, and electrocardiograms.<br>- Extent of exposure of the different treatment agents.<br>- Changes from baseline in QOL.;Timepoint(s) of evaluation of this end point: Endpoints will be evaluated in the timepoints listed in the protocol