Phase III Xevinapant (Debio 1143) and Radiotherapy in Resected LA SCCHN, High Risk, Cisplatin-ineligible Participants (XRAY VISION)

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05386550

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

700

Enrollment

Locations

Arms

100.8

Anticipated Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the superior efficacy of Xevinapant (Debio 1143) versus placebo when added to radiotherapy in the treatment of high-risk participants with resected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are ineligible to receive cisplatin-based chemoradiation concurrently. Study details include: Study duration: Participants will be followed until the last on-study participant reaches his/her 60-month post-randomization visit, a decision to end the study has been triggered, or until premature discontinuation from study, whichever occurs first. Treatment duration: 18 weeks, consisting of six 3-week cycles. Health measurement/observation: Improved Disease-Free Survival. Visit frequency: Weekly visit during combination therapy period, once every 3 weeks during monotherapy period, and every 3, 4, or 6 months during the Disease-Free Survival Follow-up period in Year 1, 2 and 3, or 4 and 5 (with telephone contact in between), respectively, and every 3 months (telephone visits allowed) during the Overall Survival Follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Xevinapant (Debio 1143) Radiation: IMRT Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, 2-arm Phase III Study to Assess Efficacy and Safety of Xevinapant and Radiotherapy Compared to Placebo and Radiotherapy for Demonstrating Improvement of Disease-free Survival in Participants With Resected Squamous Cell Carcinoma of the Head and Neck, Who Are at High Risk for Relapse and Are Ineligible for High-dose Cisplatin (XRAY VISION)

Anticipated Study Start Date :

Aug 31, 2022

Anticipated Primary Completion Date :

Jun 25, 2027

Anticipated Study Completion Date :

Jan 25, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Xevinapant (Debio 1143) + IMRT	Drug: Xevinapant (Debio 1143) Participants will receive 3 cycles of oral solution of Xevinapant (Debio 1143) at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with radiotherapy followed by 3 cycles of monotherapy of Xevinapant (Debio 1143) at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks). Radiation: IMRT Participants will receive 66 Gy of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week.
Placebo Comparator: Arm B: Placebo + IMRT	Radiation: IMRT Participants will receive 66 Gy of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week. Drug: Placebo Participants will receive 3 cycles of oral solution of placebo matched to Xevinapant (Debio 1143) once daily from Day 1 to 14 per 3-week cycle in combination with radiotherapy followed by 3 cycles of monotherapy of placebo matched to Xevinapant (Debio 1143) from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).

Arm

Intervention/Treatment

Experimental: Arm A: Xevinapant (Debio 1143) + IMRT

Drug: Xevinapant (Debio 1143)

Participants will receive 3 cycles of oral solution of Xevinapant (Debio 1143) at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with radiotherapy followed by 3 cycles of monotherapy of Xevinapant (Debio 1143) at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).

Radiation: IMRT

Participants will receive 66 Gy of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week.

Placebo Comparator: Arm B: Placebo + IMRT

Radiation: IMRT

Participants will receive 66 Gy of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week.

Drug: Placebo

Participants will receive 3 cycles of oral solution of placebo matched to Xevinapant (Debio 1143) once daily from Day 1 to 14 per 3-week cycle in combination with radiotherapy followed by 3 cycles of monotherapy of placebo matched to Xevinapant (Debio 1143) from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).

Outcome Measures

Primary Outcome Measures

Disease-Free Survival (DFS) [Time from randomization to the first occurrence of death from any cause or objective disease recurrence, assessed up to 5 years]

Secondary Outcome Measures

Overall Survival (OS) [Time from randomization to death from any cause, assessed up to 5 years]
Time to Subsequent Cancer Treatments [Time from randomization to the start of first subsequent cancer treatment, assessed up to 5 years]
Number of Participants with Adverse Events (AEs) and Treatment-related AEs [Time from randomization until end of study (up to 5 years)]
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN35) Score [Baseline up to follow-up (5 years)]
Change from Baseline in European Organization for research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Score [Baseline up to follow-up (5 years)]
Change from Baseline in EuroQOL 5 Dimension 5 Level Health-Related Quality of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS) [Baseline up to follow-up (5 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
Participants with histologically confirmed squamous cell carcinoma with one of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx. Participants have received surgery with curative intent on these sites in the past 4 to 8 weeks before start of treatment (Cycle 1 Day 1)
Oropharynx (OPC) participants must have known human papillomavirus (HPV) status as determined by p16 expression using immunohistochemistry (ICH)
Participants with no residual disease by computed tomography (CT) and 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography (18F-FDG-PET) and have a high risk of relapse with 1 or 2 of the following criteria, confirmed by local histopathology: • nodal extra-capsular extension (ECE) and positive resection margins (R1 or close margin less than or equal to (<=) 1 millimeter (mm)
Are unfit to receive high-dose cisplatin by meeting one or more of the following criteria: 30 < estimated glomerular filtration rate (eGFR) < 60 milliliter per minute per 1.73 meter square (mL/min /1.73 m^2); History of hearing loss, defined as Grade >= 2 audiometric hearing loss. An audiogram is not required if one of the other criteria meets unfitness to receive high-dose cisplatin; Peripheral neuropathy > = Grade 2 and if >= 70 years, unfit according to G8 questionnaire (Score <= 14)
Participants with adequate hematologic and hepatic function as defined in the protocol
Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
Participant with incomplete surgery
Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity, salivary, thyroid or parathyroid gland, skin or unknown primary site
Prior definitive, neoadjuvant, concurrent or adjuvant (C)RT to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents
Participation in any clinical study within 28 days prior to screening or during participation in this study
Known contraindication to undergoing positron emission tomography with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and contrast-enhanced CT scans
Known allergy to Xevinapant (Debio 1143) or any excipient known to be present in Xevinapant (Debio 1143) or in the placebo formulation
Other protocol-defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
2	Montefiore Medical Center Radiology	Bronx	New York	United States	10461
3	University of Pittsburgh Medical Center Health System - UPMC Department of Dermatology	Pittsburgh	Pennsylvania	United States	15219
4	Greenville Hospital System University Medical Center (ITOR) - Upstate Affiliate Organization	Greenville	South Carolina	United States	29605-4653
5	CEMAIC - Centro Medico Privado	Las Margaritas		Argentina
6	Clinica Viedma S.A.	Viedma		Argentina
7	Krankenhaus der barmherzigen Schwestern Linz - Abteilung für HNO	Linz		Austria
8	LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie	Salzburg		Austria
9	Cliniques Universitaires Saint-Luc - STL	Bruxelles		Belgium
10	CHU UCL Namur - Sainte-Elisabeth	Namur		Belgium
11	Hospital de Câncer de Barretos - Fundação Pio XII	Barretos		Brazil
12	Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer	Curitiba		Brazil
13	CRIO - Centro Regional Integrado de Oncologia	Fortaleza		Brazil
14	Oncosite - Centro de Pesquisa Clinica e Oncologia	Ijuí		Brazil
15	Instituto de Cancer de Londrina	Londrina		Brazil
16	HGB - Hospital Giovanni Battista - Mãe de Deus Center	Porto Alegre		Brazil
17	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil
18	Hospital Ernesto Dornelles	Porto Alegre		Brazil
19	Hospital Nossa Senhora da Conceicao	Porto Alegre		Brazil
20	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre		Brazil
21	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo André		Brazil
22	INCA - Instituto Nacional de Câncer	Sao Goncalo		Brazil
23	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira	Sao Paulo		Brazil
24	Hunan Cancer Hospital	Changsha		China
25	West China Hospital, Sichuan University	Chengdu		China
26	Fujian Cancer Hospital	Fuzhou		China
27	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou		China
28	Zhejiang Cancer Hospital	Hangzhou		China
29	Shandong Cancer Hospital	Jinan		China
30	Union Hospital, Tongji Medical College of Huazhong University of Science & Technology	Wuhan		China
31	Northern Jiangsu People's Hospital	Yangzhou		China
32	Fakultni nemocnice Olomouc - Dept of Onkologicka klinika	Olomouc		Czechia
33	Fakultni nemocnice Bulovka - Dept of Radiodiagnosticka klinika	Praha 8		Czechia
34	Centre Azureen Cancerologie - Service De Radiotherapie	Mougins		France
35	Hopital Tenon - service radiologie et imagerie medicale	Paris cedex		France
36	CHU Tours - Hôpital Bretonneau - Service d'Oncologie Médicale	Tours		France
37	Institut Gustave Roussy - Oncologie Médicale	Villejuif		France
38	Universitaetsklinikum Schleswig-Holstein - Campus Kiel - Klinik für diagnostische Radiologie	Kiel		Germany
39	Universitaetsklinikum Regensburg - Innere Medizin III Haematologie, Onkologie	Regensburg		Germany
40	Universitaetsmedizin Rostock - Klinik und Poliklinik für Strahlentherapie	Rostock		Germany
41	Ospedale Oncologico Armando Businco - Divisione di Oncologia Medica II	Cagliari		Italy
42	Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica	Firenze		Italy
43	IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - U. Operativa di Immunoterapia e Terapia Cellulare	Meldola		Italy
44	Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Tumori della Testa e del Collo	Milano		Italy
45	IEO Istituto Europeo di Oncologia - Divisione Oncologia Medica	Milano		Italy
46	Ospedale San Raffaele - U.O. di Oncologia Medica	Milano		Italy
47	A.O.U. Policlinico di Modena - U.O. Oncologia	Modena		Italy
48	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli" - Dipartimento Oncologia	Napoli		Italy
49	Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A	Napoli		Italy
50	IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2	Padova		Italy
51	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza - U.O.C. di Oncologia B	Roma		Italy
52	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Radioterapia 1	Roma		Italy
53	Hyogo Cancer Center - Dept of Head and Neck Surgery	Akashi-shi		Japan
54	National Cancer Center Hospital - Dept of Gastroenterology	Chuo-ku		Japan
55	NHO Kyushu Cancer Center - Dept of Head and Neck Surgery	Fukuoka-shi		Japan
56	Saitama Medical University International Medical Center - Dept of Otorhinolaryngology/ Head and Neck Surgery	Hidaka-shi		Japan
57	Hiroshima University Hospital - Dept of Otorhinolaryngology/ Head and Neck Surgery	Hiroshima-shi		Japan
58	National Cancer Center Hospital East - Dept of Head and Neck Medical Oncology	Kashiwa-shi		Japan
59	Cancer Institute Hospital of JFCR - Dept of Medical Oncology	Koto-ku		Japan
60	NHO Shikoku Cancer Center - Dept of Head and Neck Surgery	Matsuyama-shi		Japan
61	Aichi Cancer Center Hospital - Dept of Head and Neck Surgery	Nagoya-shi		Japan
62	Okayama University Hospital - Dept of Otorhinolaryngology	Okayama-shi		Japan
63	Osaka International Cancer Institute - Dept of Head and Neck Surgery	Osaka-shi		Japan
64	Kindai University Hospital - Dept of Oncology	Osakasayama-shi		Japan
65	Hokkaido University Hospital - Dept of Otorhinolaryngology	Sapporo-shi		Japan
66	NHO Hokkaido Cancer Center - Dept of Oral Oncology Surgery	Sapporo-shi		Japan
67	Yokohama City University Hospital - Dept of Otorhinolaryngology	Yokohama-shi		Japan
68	Chonnam National University Hwasun Hospital	Hwasun-gun		Korea, Republic of
69	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of
70	Konkuk University Medical Center	Seoul		Korea, Republic of
71	Seoul National University Hospital	Seoul		Korea, Republic of
72	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of
73	Pusan National University Yangsan Hospital	Yangsan-si		Korea, Republic of
74	Hospital de Braga - Serviço de Oncologia Medica	Braga		Portugal
75	S.C Medisprof S.R.L - parent	Cluj-Napoca		Romania
76	S.C Radiotherapy Center Cluj S.R.L - Parent	Comuna Floresti		Romania
77	S.C Oncocenter Oncologie Clinica S.R.L - parent	Timisoara		Romania
78	Complejo Hospitalario Universitario Insular Materno-Infantil - Servicio de Oncologia	Las Palmas de Gran Canaria		Spain
79	Hospital Universitario Lucus Augusti - Oncology	Lugo		Spain
80	Clinica Universidad de Navarra (MAD) - Oncology Service	Madrid		Spain
81	Hospital Universitario Fundacion Jimenez Diaz - Oncology	Madrid		Spain
82	Hospital Regional Universitario de Malaga - Oncology Dept	Málaga		Spain
83	Hospital Universitario Virgen del Rocio - Oncology Service	Sevilla		Spain
84	Universitaetsspital Basel - Klinik fuer Strahlentherapie und Radioonkologie	Basel		Switzerland
85	Changhua Christian Medical Foundation Changhua Christian Hospital	ChangHua		Taiwan
86	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
87	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
88	China Medical University Hospital	Taichung		Taiwan
89	Chi Mei Hospital, Liouying	Tainan		Taiwan
90	National Cheng Kung University Hospital	Tainan		Taiwan
91	National Taiwan University Hospital	Taipei		Taiwan
92	Taipei Veterans General Hospital	Taipei		Taiwan
93	Chang Gung Memorial Hospital,Linkou	Taoyuan		Taiwan
94	Adana City Hospital - Parent Account	Adana		Turkey
95	Gazi University Medical Faculty - Parent Account	Ankara		Turkey
96	Trakya University Medical Faculty - Parent Account	Edirne		Turkey
97	Inonu Uni. Med. Fac. - Medical Oncology	Malatya		Turkey
98	Mount Vernon Hospital - Dept of Oncology	Northwood		United Kingdom