Study Stopped
A phase III trial of the investigational agent failed to pass futility boundaries at interim analysis
Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer
Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features
3 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Apr 2024
Typical duration for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 10, 2023
CompletedFirst Posted
Study publicly available on registry
October 16, 2023
CompletedStudy Start
First participant enrolled
April 12, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2028
July 25, 2024
December 1, 2023
4.1 years
October 10, 2023
July 24, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Disease free survival (DFS)
Assuming an exponential distribution for DFS, this hypothesis corresponds to an increase in the 2-year DFS rate from 55% (assumed rate in the control arm) to 70%. Full information required will be a total of 100 DFS events. An intention to treat analysis including all randomized patients will be used. Kaplan-Meier estimates will be used to estimate the DFS distributions. A log-rank test with a one-sided 10% type I error will be used for the comparison between the arms.
From the date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed at 2 years
Secondary Outcomes (2)
Overall survival (OS)
From the date of randomization to the date of death from any cause, assessed at 2 years
Incidence of adverse events
Up to 30 days post completion of treatment
Study Arms (2)
Arm A (chemoradiation)
ACTIVE COMPARATORPatients 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.
Arm B (chemoradiation, xevinapant)
EXPERIMENTALPatients 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
Undergo blood sample collection
Given IV
Undergo chest x-ray
Given IV
Undergo CT and/or PET-CT
Undergo IGRT
Undergo IMRT
Undergo MRI
Undergo PET-CT
Given PO
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 18 years of age
- Patient must have stage III or IVA or IVB HPV-negative squamous cell carcinoma of the head and neck (HNSCC) by American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition criteria
- Patient must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to randomization
- 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
- Patient must have tumor origin site in the oral cavity, oropharynx, larynx, or hypopharynx
- Patient must have received no prior treatment for HNSCC with the exception of curative intent surgical resection
- Patient must have imaging consisting of CT of the head, neck and chest within 10 weeks prior to randomization to confirm there is no evidence of disease
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
- All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
- 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)
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ECOG-ACRIN Cancer Research Grouplead
- National Cancer Institute (NCI)collaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Heath D Skinner
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 10, 2023
First Posted
October 16, 2023
Study Start
April 12, 2024
Primary Completion (Estimated)
May 31, 2028
Study Completion (Estimated)
May 31, 2028
Last Updated
July 25, 2024
Record last verified: 2023-12