Trial Title:
A Study of Xevinapant With Cisplatin and Radiation Therapy After Surgery in People With Head and Neck Cancer
NCT ID:
NCT06145412
Condition:
Head and Neck Cancer
Conditions: Official terms:
Head and Neck Neoplasms
Cisplatin
Conditions: Keywords:
Xevinapant
Cisplatin
Radiotherapy
23-044
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single arm phase II.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Xevinapan
Description:
Xevinapant (oral dose of 200mg per day on days 1-14 every 21 days for 3 cycles)
Arm group label:
Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin (2-3 cycles, with 100mg/m2 per cycle q3 weeks)
Arm group label:
Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy
Intervention type:
Radiation
Intervention name:
External beam
Description:
60 - 66 Gy in 2 Gy fractions for patients without gross disease and 70 Gy for patients
with early recurrence) with concurrent cisplatin (40 mg/m2 once weekly)
Arm group label:
Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy
Summary:
The purpose of this study is to test whether treatment with Xevinapant added to standard
chemoradiation after surgery is an effective treatment for people with high-risk head and
neck cancers.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 on the day of signing of the consent form
- ECOG 0-1
- Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy,
or jejunostomy placed
- Squamous cell carcinoma of the head and neck (excluding lip) *
o Eligible primary tumor sites will include the maxillary sinus, oral cavity,
HPV-negative oropharynx, larynx, and hypopharynx.
- Gross total resection of known disease at the time of surgery within 10 weeks of
registration. All efforts will be made to begin treatment within 6 weeks of surgery.
- At least one of the following criteria
- Close surgical margin (<5mm) AND ≥2 additional intermediate risk factors (T3 or
T4, multiple lymph nodes, LVI, PNI)
- Positive margins not eligible for re-resection (defined as <1mm)
- Extranodal extension
- Evidence of early gross recurrence on radiation planning scans after definitive
intent surgical resection Patients with evidence of gross locoregional disease
at the time of radiation are strongly advised to have biopsy confirmation. This
requirement may be waived by the PI or the co-PIs. If a biopsy is not
performed, patients must meet one of the other entry criteria (close surgical
margin and 2 or more additional intermediate risk factors; positive margins not
eligible for re-resection; extranodal extension).
- Adequate hematologic, renal, and hepatic function as indicated by:
- Absolute neutrophil count ≥ 1 500 cells/μL
- Platelets ≥ 100 000 cells/μL
- Hemoglobin ≥ 9.0 g/dL (blood transfusions during screening are permitted)
- AST and ALT ≤ 3.0 × upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 × ULN (up to 2.0 × ULN is allowed if the direct bilirubin
level is normal, and the elevation is limited to indirect bilirubin).
- Adequate renal function within 30 days prior to registration, defined as follows:
Creatinine clearance (CC) ≥ 60 ml/min determined by 24-hour collection or estimated by
Cockcroft-Gault formula:
- CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)]
- CCr female = 0.85 x (CrCl male) 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.
- Women of childbearing potential must agree to use highly effective
contraceptive method(s). from ICF signature to 6 months after the last
administration of chemotherapy or 3 months after last dose of xevinapant,
whichever is the latest.
- Non-sterilized males who are sexually active with a female partner of
childbearing potential must agree to use condom and spermicide from ICF
signature to 6 months after the last administration of chemotherapy or 3 months
after the last dose of xevinapant, whichever is the latest.
- Because male condom and spermicide is not a highly effective contraception
method, it is required that female partners of a male study subject use highly
effective contraceptive method(s) throughout this period.
- Male subjects must refrain from donating sperm during the clinical study and
for 6 months after the last administration of chemotherapy or 3 months after
the last dose of xevinapant, whichever is the latest.
- If not done previously, cryopreservation of sperm prior to receiving
chemotherapy or xevinapant is advised to male patients with a desire to have
children.
Exclusion Criteria:
- Metastatic disease
- Prior head and neck radiation
- Peripheral Neuropathy ≥ grade 2
- Hearing Impairment ≥ grade 2
- On-going wound infection, fistula, flap failure
- Use within 14 days prior to randomization or requirement for ongoing treatment
with any drug(s) on the prohibited medication list (see below).
- 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.
- Known chronically active HBV or HCV infection. If unknown status, the following
tests are to be performed and subjects with positive serology must be excluded:
- HBV screening tests: both HBV sAg and Anti-HepB core IgG.
- HCV screening tests: both HCV-antibody and positive viral load HCV-RNA by
PCR.
- Other infections (viral and/or bacterial and/or mycotic) requiring
systemic treatment.
- Live-attenuated vaccinations within 30 days prior to first investigational
treatment administration.
Ongoing uncontrolled infection requiring intravenous antibiotic therapy within 1 week
prior to randomization.
- 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. No albumin transfusions are allowed within 2 weeks before
randomization.
- Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic
lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other
autoimmune diseases) requiring ongoing treatment with anti-TNF medication.
- 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.
- Known allergy to Xevinapant or any excipient known to be present in the formulation.
- Non-compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C).
- Treatment with an investigational agent or use of an investigational device within 4
weeks of the first dose of study treatment.
- Known gastrointestinal disorder with clinically established malabsorption syndrome
and major gastrointestinal surgery that may limit oral absorption.
- 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.
- Impaired cardiovascular function or clinically significant cardiovascular diseases,
including any of the following:
- Ongoing or history of uncontrolled or symptomatic ischemic myocardiopathy
within 6 months prior to randomization.
- Known left ventricular ejection fraction < 50%).
- History of myocardial infarction, or severe/unstable angina, within 6 months
prior to randomization.
- New York Heart Association grade ≥ 3 congestive heart failure.
- Congenital long QT syndrome.
- Family history of long QT syndrome.
- Symptomatic pulmonary embolism within 6 months prior to randomization.
- Ongoing or known history of transient ischemic attacks or stroke within 6
months prior to randomization.
- QTc using Fridericia's formula (QTcF) interval > 450 ms for males and > 470 ms
for females Symptomatic pulmonary disease requiring continuous or intermittent
oxygen supply.
- 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.
- 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.
- Lack of ability to understand and willingness to sign a written informed consent and
complete questionnaires.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Monmouth
Address:
City:
Middletown
Zip:
07748
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Bergen
Address:
City:
Montvale
Zip:
07645
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack
Address:
City:
Commack
Zip:
11725
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Westchester
Address:
City:
Harrison
Zip:
10604
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Nassau
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Start date:
November 16, 2023
Completion date:
November 2026
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06145412
https://www.mskcc.org/
