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

JRCT ID: jRCT2011220014

Registered date:10/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: resected SCCHN, who are at high risk for relapse and are ineligible for high-dose cisplatin
• Date of first enrollment: 15/09/2022
• Target sample size: 700
• Countries of recruitment: United States,Japan,Argentina,Japan,Brazil,Japan,China,Japan,South Korea,Japan,Taiwan,Japan,Belgium,Japan,Germany,Japan,Italy,Japan,Portugal,Japan,Romania,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Experimental arm:
Concomitant chemo-radiation therapy period (Cycles 1-3):
-Xevinapant: Xevinapant administrated as oral solution from Day 1 to 14, every 21-day cycle.
-Intensity Modulation Radiation Therapy (IMRT): 66 Gy given in 33 fractions over 7 weeks.
Monotherapy period (Cycles 4-6):
-Xevinapant: Xevinapant administrated as oral solution from Day 1 to 14, every 21-day cycle.

Active comparator arm:
Concomitant chemo-radiation therapy period (Cycles 1-3):
-Placebo: Matched placebo administrated as oral solution from Day 1 to 14, every 21-day cycle.
-Intensity Modulation Radiation Therapy (IMRT): 66 Gy given in 33 fractions over 7 weeks.
Monotherapy period (Cycles 4-6):
-Placebo: Matched placebo administrated as oral solution from Day 1 to 14, every 21-day cycle.

Outcome(s)

• Primary Outcome: Disease-Free Survival (DFS)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Have ECOG PS 0-1
2. Participants with HPV-negative oropharynx cancers as determined by testing p16 expression using immunohistochemistry (IHC), with oral cavity, hypopharynx or larynx cancers with the following pathological staging (pTNM stage according to the American Joint Committee on Cancer AJCC/TNM Staging System 8th Edition):
-pIII or
-pIVA or pIVB
OR
Participants with HPV-positive oropharynx cancers, as determined by testing p16 expression using IHC, must be smokers > 25 Pack-Year, and must have the following pTNM stage (according to the AJCC/TNM Staging System 8th Edition):
-pT3 and pN2 or
-pT4 and pN2
OPC participants must have known HPV status as determined by p16 expression using IHC
3. Are unfit to receive high-dose cisplatin by meeting one or more of the following criteria:
-30 < eGFR < 60 mL/min /1.73 m2 (using the CKD-EPI creatinine formula)
-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
-If ? 70 years, unfit according to G8 questionnaire (Score <= 14)
4. Have adequate hematologic and hepatic function
5. Other

Exclude criteria

1.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.
2.Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity, salivary, thyroid or parathyroid gland, skin or unknown primary site.
3.Participant with incomplete surgery i.e. R2 resection
4.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.
5.Participation in any clinical study within 28 days prior to screening or during participation in this study.
6.Known contraindication to undergoing positron emission tomography with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and contrast-enhanced CT scans.
7.Known allergy to xevinapant or any excipient known to be present in xevinapant or in the placebo formulation.
8.Other

Related Information

• Primary Sponsor: Suzuki Tomoya