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Head and Neck Squamous Cell CarcinomaPhase 2NCT06084845

Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer

A Phase 2 study testing Biospecimen Collection, Carboplatin and Chest Radiography in people with Head and Neck Squamous Cell Carcinoma and Hypopharyngeal Squamous Cell Carcinoma, run by ECOG-ACRIN Cancer Research Group.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Carboplatin and Chest Radiography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
12 Apr 2024to 31 May 2028
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 31Show fewer
  • 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)
  • 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 a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • 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 have had a live-attenuated vaccine within 30 days prior to randomization
  • Patient must not have a known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery that may limit oral absorption
  • Patient must not have taken any agents on the prohibited medication list within 14 days prior to randomization or require any of these agents for ongoing treatment while on protocol treatment
  • Patient must not have active, uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other autoimmune diseases) requiring ongoing treatment with anti-tumor necrosis factor (TNF) medication
  • Patient must have had a pre-surgical or other baseline electrocardiogram (EKG) report within 6 months prior to randomization indicating a corrected QT (QTc) using Fridericia's formula (QTcF) interval < 450 ms for males and < 470 ms for females
  • 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 products

Who cannot join

None listed.

About this study

Official title: Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. To evaluate the following endpoints: Overall Survival (OS), rates of distant metastasis (DM), local regional control (LRR).

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.

Being tested
Biospecimen Collection, Carboplatin, Chest Radiography, Cisplatin, Computed Tomography
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Chest RadiographyProcedure or surgery

    Also called Chest X-ray

    Undergo chest x-ray

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT and/or PET-CT

  • Image Guided Radiation TherapyRadiation

    Also called IGRT, image-guided radiation therapy, Image-Guided Radiotherapy

    Undergo IGRT

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET-CT

  • XevinapantDrug

    Also called AT-406, D1143, Debio 1143, Debio-1143

    Given PO

Study groups in NCT06084845
Study groupRoleWhat they receive
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.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Chest Radiography; Drug: Cisplatin; Procedure: Computed Tomography; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
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.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Chest Radiography; Drug: Cisplatin; Procedure: Computed Tomography; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Xevinapant

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Overall survival (OS)

    Assuming a 2-year OS rate of 69% in the control arm, maintaining a one-sided significance level of 10%, there is 80% power to detect a hazard ratio of 1.66, for the comparison of control arm versus experimental arm. Assuming an exponential distribution for OS, this hypothesis corresponds to an increase in the 2-year OS rate from 69% to 80%. Full information will be a total of 72 OS events.

    Measured: From the date of randomization to the date of death from any cause, assessed at 2 years

  2. Incidence of adverse events

    All treated patients will be evaluated for toxicity (using the Common Terminology Criteria for Adverse Events) regardless of eligibility. Toxicity will be examined by arm and compared using the Fisher's exact test.

    Measured: Up to 30 days post completion of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2023
  2. Study start12 Apr 2024 (estimated)
  3. Primary completion31 May 2028 (estimated)
  4. Study completion31 May 2028 (estimated)

Why it stopped: A phase III trial of the investigational agent failed to pass futility boundaries at interim analysis

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06084845
Sponsor's protocol ID
EA3222
Other IDs
NCI-2023-06677, EA3222, EA3222, U10CA180820
Status last verified
Dec 2023
First submitted
10 Oct 2023
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Carboplatin and Chest Radiography in people with Head and Neck Squamous Cell Carcinoma and Hypopharyngeal Squamous Cell Carcinoma, run by ECOG-ACRIN Cancer Research Group.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease free survival (DFS) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06084845.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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