Clinical Trial Finder
Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer
Study Purpose
This phase II trial compares the effect of usual radiation therapy with cisplatin/carboplatin (chemoradiation) to the addition of xevinapant with chemoradiation in patients with head and neck cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Xevinapant is a first-in-class antagonist of inhibitor of apoptosis (programmed cell death) proteins (IAPs), which leads to tumor cell death and enhances tumor cell sensitivity to chemotherapy and radiotherapy. Giving xevinapant with chemoradiation may be more effective in preventing head and neck cancer from growing or spreading than chemoradiation alone.
Recruitment Criteria
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
Inclusion Criteria:
- - Patient must have evidence of high-risk features on final postoperative pathology
including positive margins (R1) and/or extranodal extension.
Patients with gross residual disease are not eligible.- - A patient of childbearing potential is defined as anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone
a hysterectomy or bilateral oophorectomy; or 3) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months)
- Patient must not expect to conceive or father children by using accepted and effective
method(s) of contraception or by abstaining from sexual intercourse for the duration
of their participation in the study and continue contraception measures for 6 months
after the last dose of cisplatin or carboplatin and for 3 months after the last dose
of xevinapant.
Patient must not breast-feed while on protocol treatment and for one month after the last dose of any protocol treatment. Patient must not donate sperm while on protocol treatment.- - Patient must have the ability to understand and the willingness to sign a written
informed consent document.
Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.- - White blood cell (WBC) ≥ 3,000/mcL (obtained ≤ 14 days prior to protocol
randomization)
- Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained ≤ 14 days prior to protocol
randomization)
- Platelets ≥ 100,000/mcL (obtained ≤ 14 days prior to protocol randomization)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 14 days
prior to protocol randomization)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤
3.0 × institutional ULN (obtained ≤ 14 days prior to protocol randomization)
- Creatinine clearance ≥ 60 mL/min (estimated using Cockcroft-Gault method or measured)
(obtained ≤ 14 days prior to protocol randomization)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of randomization are eligible for
this trial.
Patients with HIV must have viral load monitored as clinically indicated.- - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
Patients with non-compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C) are not eligible.- - Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured.
For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Patients with non-compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C) are not eligible.- - Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification.
To be eligible for this trial, patients should be class 2B or better.- - Patient must not be on any concomitant medication known to prolong the QTcF interval
that cannot be discontinued or replaced by safe alternative medication within 7 days
prior to randomization.
- Patient must not have a known allergy to xevinapant, cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these productsTrial Details
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
The person who is responsible for the scientific and technical direction of the entire clinical study.
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
PRIMARY OBJECTIVE:
- I. To evaluate whether adding xevinapant to post-operative adjuvant treatment with cisplatin
+ radiation followed by xevinapant monotherapy in patients with surgically resected head and
neck squamous cell carcinoma (HNSCC) who have extra-nodal extension (ENE) and/or positive
margins will improve the disease-free survival (DFS).
SECONDARY OBJECTIVES:- II. To assess safety and tolerability of treatment intensification.
OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive cisplatin or carboplatin intravenously (IV) over 30-60 minutes once a week (QW) for 6 doses with concurrent intensity-modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up. ARM B: Patients receive cisplatin or carboplatin IV over 30-60 minutes QW for 6 doses with concurrent IMRT and IGRT five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive xevinapant orally (PO) on days 1-14 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, PET-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up. Upon completion of study treatment, patients are followed up at 30 days and every 6 months if patient is < 3 years from randomization and every 12 months if patient is 3-5 years from randomization.Arms
Active Comparator: Arm A (chemoradiation)
Patients receive cisplatin or carboplatin IV over 30-60 minutes QW for 6 doses with concurrent IMRT and IGRT five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, PET-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up.
Experimental: Arm B (chemoradiation, xevinapant)
Patients receive cisplatin or carboplatin IV over 30-60 minutes QW for 6 doses with concurrent IMRT and IGRT five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive xevinapant PO on days 1-14 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, PET-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up.
Interventions
Procedure: - Biospecimen Collection
Undergo blood sample collection
Drug: - Carboplatin
Given IV
Procedure: - Chest Radiography
Undergo chest x-ray
Drug: - Cisplatin
Given IV
Procedure: - Computed Tomography
Undergo CT and/or PET-CT
Radiation: - Image Guided Radiation Therapy
Undergo IGRT
Radiation: - Intensity-Modulated Radiation Therapy
Undergo IMRT
Procedure: - Magnetic Resonance Imaging
Undergo MRI
Procedure: - Positron Emission Tomography
Undergo PET-CT
Drug: - Xevinapant
Given PO
Contact Information
This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:
For additional contact information, you can also visit the trial on clinicaltrials.gov.
Privacy Overview