This study has been transitioned to CTIS with ID 2023-508528-36-00 check the CTIS register for the current data. The purpose of this study is to demonstrate improvement in Disease-Free Survival (DFS) with xevinapant compared to placebo when added to…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Disease-Free Survival (DFS).
Secondary outcome
1. Overall Survival (OS)
2. Time to Subsequent Cancer Treatments
3. Occurrence of Adverse Events (AEs) and Treatment-related AEs
4. Change from Baseline in European Organization for Research and Treatment of
Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN35) Score
5. Change from Baseline in European Organization for research and Treatment of
Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Score
6. Change from Baseline in EuroQOL 5 Dimension 5 Level Health-Related Quality
of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS)
Background summary
Xevinapant is an antagonist of IAPs that has been shown in nonclinical in vitro
and in
vivo models to have both chemo- and radiosensitizing potential, as well as
immunomodulatory
potential. In unresectable LA SCCHN patients, the addition of xevinapant to
standard of care chemoradiotherapy recently showed a statistically significant
and clinically meaningful improvement in locoregional control at 18 months
compared to placebo and standard of care alone.
The purpose of this study is to demonstrate the superior efficacy of xevinapant
vs placebo when added to radiotherapy in the treatment of high-risk
participants with resected LA SCCHN who are ineligible to receive
cisplatin-based chemoradiation concurrently.
Study objective
This study has been transitioned to CTIS with ID 2023-508528-36-00 check the CTIS register for the current data.
The purpose of this study is to demonstrate improvement in Disease-Free
Survival (DFS) with xevinapant compared to placebo when added to RT
irrespective of subsequent anticancer therapy.
Study design
This is a multicenter, randomized double-blind, placebo-controlled, 2-arm,
parallel-group Phase III study.
Intervention
Participants who meet the eligibility criteria will be enrolled and randomized
in a 1:1 ratio, using permuted block allocation to Arm A or Arm B and will
receive the following treatments:
• Arm A: 3 cycles of xevinapant (oral solution 200 mg/day from Day 1 to 14, per
3-week cycle)
+ IMRT (66 Gy in 33 fractions, 2 Gy/fraction, 5 days/week), followed by 3
cycles of
monotherapy of xevinapant (oral solution 200 mg/day from Day 1 to 14, per
3-week cycle)
OR
• Arm B: 3 cycles of placebo (matching oral solution from Day 1 to 14, per
3-week cycle) +
IMRT (66 Gy in 33 fractions, 2 Gy/fraction, 5 days/week), followed by 3 cycles
of monotherapy
of placebo (matching oral solution from Day 1 to 14, per 3-week cycle).
• 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.
• 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.
Study burden and risks
Subject*s participation in this study will last 5 years and consists of a
screening period, treatment period and a follow-up period.
During the treatment period, subjects will need to visit the study site for 5
days every week for the first 6.5 weeks (which may be extended to 9 weeks only
if radiotherapy is put on hold within the initial 6.5 weeks). There after
subjects will need to visit the study site once every 3 weeks. During the
follow-up period, subjects will need to visit the study site at Month 7, 9, and
12 for the first year, every 4 months for the 2nd to 3rd years, and every 6
months for 4th to 5th years, or earlier if there is disease progression.
If there is disease progression or subject has completed 4.5 years of
disease-free health status follow-up, then subject may need to visit the study
center or receive telephone calls every 3 months until approximately 5 years
after the last participant receives the study medication or subject is no
longer able to continue in the study.
Aside from the intervention described above, participation in this study
involves blood draws at multiple visits, biopsy at at time of relapse,
radiation exposure through CT & PET scan, and might involve radiation exposure
through MRI scans. It also may involve an audiometry test and a dental exam.
Participants will be subjected to: questions regarding medical history, use of
concomitant medications/procedures and adverse events; urine sampling;
measurement of vital signs; physical examination; ECOG performance status; ECGs
and patient reported outcomes questionnaires.
Subjects will be expected to come to their visits, to not take part in
other medical studies, keep their appointments for visits, follow instructions
from the study team, keep a patient card with them at all times, not donate
blood/sperm/ova and to use appropriate forms of contraception. Subjects will
also be asked to complete a diary daily with questions about their Xevinapant/
Placebo intake.
The side effects listed below are those reported in other clinical medical
scientific studies when xevinapant was given as a single drug or in
combinations with various other drugs; however, a causal link to xevinapant has
not been proved. In addition, there might be side effects not yet known that
may occur. It is possible that giving xevinapant with radiotherapy will result
in more severe or new side effects or that side effects will worsen more
rapidly than expected. Some side effects of xevinapant may occur anytime during
treatment or even after the treatment has ended.
Common (in more than 5 up to 100 in 100 people) side effects of xevinapant
include: nausea, vomiting, stomatitis, dry mouth, decreased appetite, diarrhea,
constipation, asthenia, fatigue, anemia, Alanine aminotransferase (ALT)
increase (abnormal liver tests), Aspartate aminotransferase (AST) increase
(abnormal liver tests), Hyperlipasemia/Lipase increase, rash, pruritus.
Based on current available efficacy and safety data available for xevinapant
treatment, including the combination with chemoradiotherapy (CRT) and/or
immunotherapy, and for Radiotherapy (RT) alone, the benefit/risk assessment for
a study combining xevinapant with Radiotherapy (RT) is expected to be positive.
Frankfurter Str. 250 Frankfurter Str. 250
Darmstadt 64293
DE
Frankfurter Str. 250 Frankfurter Str. 250
Darmstadt 64293
DE
Listed location countries
Age
Inclusion criteria
• Participants with Eastern Cooperative Oncology Group Performance Status (ECOG
PS) 0-2 and able to tolerate standard of care IMRT treatment according to
Investigator assessment.
• 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) or magnetic
resonance imaging (MRI) 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: estimated glomerular filtration rate (eGFR) < 60
milliliter per minute per 1.73 meter square (mL/min /1.73 m^2); History of
hearing impairment, defined as Grade >= 2 audiometric hearing loss or tinnitus
Grade >=2. 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) or ineligible
for cisplatin treatment due to age limit to national guidelines
• Participants with adequate hematologic, renal 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 interventional 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
• Participants with recurrent or metastatic disease
• Other protocol-defined exclusion criteria could apply
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508528-36-00 |
| EudraCT | EUCTR2022-001144-18-NL |
| ClinicalTrials.gov | NCT05386550 |
| CCMO | NL82563.056.22 |