Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Cetuximab

Cisplatin

Antineoplastic Agents, Immunological

3 cycles of placebo (matching oral solution from Day 1 to 14, per 3-week cycle) + IMRT (69.96 Gy in 33 fractions, 2.12 Gy/fraction) + cetuximab (loading dose of 400 mg/m² IV on Day -7, followed by weekly dose of 250 mg/m² IV until the end of the RT), followed

3 cycles of xevinapant (oral solution 200 mg/day from Day 1 to 14, per 3-week cycle) + IMRT (69.96 Gy in 33 fractions, 2.12 Gy/fraction) + cetuximab (loading dose of 400 mg/m² IV on Day -7, followed by weekly dose of 250 mg/m² IV until the end of the RT), followed by 3 cycles of monotherapy of xevinapant (200 mg/day from Day 1 to 14, per 3-week cycle)

Xevinapant is a multi-IAP antagonist that blocks the activity of several IAPs including X-linked IAP (XIAP), cellular inhibitor of apoptosis proteins (cIAP) 1, cIAP2 and ML-IAP

Xevinapant

Placebo

cetuximab

IMRT (69.96 Gy in 33 fractions, 2.12 Gy/fraction)

IMRT

Jean BOURHIS, Pr

Yoann POINTREAU, Dr

Xu-Shan SUN

Xevinapant is an antagonist of inhibitor of apoptosis proteins (IAPs) that has been shown both chemo-, radiosensitizing, and immunomodulatory activities in nonclinical in vitro and in vivo squamous cell carcinoma of the head and neck (SCCHN) models. In previously untreated patients with non-resected locally advanced SCCHN, the addition of xevinapant recently showed a significant improvement of progression-free survival (PFS), overall survival (OS) and loco-regional control at 3 years after completing treatment. Thus, the purpose of this Phase III study is to demonstrate the superior efficacy to the xevinapant when it is administered in combination with radiotherapy (RT)+cetuximab compared to radiotherapy+cetuximab (SoC) + placebo in previously untreated participants with LA-SCCHN, ineligible for high-dose cisplatin defined as ≥ 200 mg/m² (projective total cumulative dose) throughout the course of the radiotherapy.

CT-RT and especially cisplatin-RT is a well-established and the most commonly used SoC for patients with LA SCCHN15. However, a large proportion of patients with LA SCCHN are not suitable for high dose platin based CT-RT for several reasons (age, medical/general conditions and or comorbidities...).

Based on recent GORTEC study, the proportion of patients unfit for receiving high-dose of cisplatin was 43% among 707 patients randomized19. In the corresponding cohort of the REACH study, the characteristics of the population (same population to be included in the XXL study) were fragile patients, unfit for high-dose cisplatin, with heavy alcohol and tobacco consumption, numerous comorbidities and a median age 67 years. In this population, there was a trend in the triplet combination of cetuximab-avelumab-RT towards improving PFS, but the triplet was also associated with increased death without previous cancer progression in the first 6 months after RT. In the control arm, the doublet of cetuximab-RT regimen was better tolerated with no excess of death. Same good tolerance was also observed with doublet treatments in both arms of the PembroRad trial (NCT02707588).

The addition of xevinapant to cetuximab is combining two complementary radiosensitizing effects that could ultimately improve the tumor control when compared to cetuximab alone. However, it is

Participants who meet the study criteria will be randomly assigned in a 1:1 ratio using minimization to Arm A or arm B

Study Comparing RT With Cetuximab + Xevinapant to RT With Cetuximab-placebo in Patients With Head and Neck Cancer

A Double-blind, Randomized, Phase III Study of Radiotherapy Combined With cetuXimab + Xevinapant Compared to Radiotherapy Combined With Cetuximab (Standard of Care) + Placebo in Patients With LA SCCHN, Unfit for High-dose Cisplatin

PFS as assessed by independent review committee (IRC) defined as the time from randomization to the first occurrence of any of the following events: death from any cause, disease progression (PD), primary treatment failure before achieving a complete response (CR) or any radiological or clinical relapse after achieving a CR.

Groupe Oncologie Radiotherapie Tete et Cou

Neoplasms, Squamous Cell

3 cycles of xevinapant (200 mg/day from Day 1 to 14, per 21-day cycle) + IMRT followed by 3 cycles of xevinapant in monotherapy (200 mg/day from Day 1 to 14, per 21-day cycle)

3 cycles of placebo (from Day 1 to 14, per 21-day cycle) + IMRT followed by 3 cycles of placebo in monotherapy (from Day 1 to 14, per 21-day cycle).

3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy

3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy

EORTC HQ

Sjoukje Oosting, Dr

Pierluigi Bonomo, Dr

This is a multicenter, randomized, placebo-controlled, triple blind, phase II study to determine the efficacy and safety of xevinapant with radiotherapy in older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of oral cavity, oropharynx, hypopharynx, or larynx.

Upon confirmation of eligibility, subjects will be enrolled and randomized in a 1:1 ratio to:

* Arm A: 3 cycles of xevinapant (200 mg/day from Day 1 to 14, per cycle) + intensive modulated radiotherapy (IMRT) followed by 3 cycles of xevinapant in monotherapy phase (200 mg/day from Day 1 to 14, per cycle)
* Arm B: 3 cycles of placebo (from Day 1 to 14, per cycle) + IMRT followed by 3 cycles of placebo in monotherapy phase (from Day 1 to 14, per cycle).

Patients will be stratified by institution, disease location/p16 status (p16 positive oropharyngeal cancer, versus others), G8 score. Three strata for the G8 will be used (\>14, versus 11-14 versus \<11).

Patients will undergo imaging in week 20 and upon clinical suspicion of progression/recurrence. Clinical examination will take place every 12 weeks in the first 3 years.

Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Radiotherapy Plus Xevinapant or Placebo in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: a Randomized Phase II Study RAVINA

To demonstrate superior efficacy in terms of locoregional event-free survival of xevinapant vs placebo when added to radical radiotherapy in older patients with LA-HNSCC.

To estimate the added value of xevinapant over RT alone in terms of response to treatment.

To estimate the added value of xevinapant over RT alone in PFS.

To estimate the added value of xevinapant over RT alone in OS.

To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms.

To assess non-inferiority of xevinapant arm compared to placebo in terms of health-related quality of life (HRQoL) as assessed by the EORTC QLQ-C30 global health/QoL and physical functioning scales.

The questionnaires employ 50 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall HRQoL. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms.

Merck KGaA, Darmstadt, Germany

European Organisation for Research and Treatment of Cancer - EORTC

Mouth and Tooth Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Mouth Neoplasms

Laryngeal Neoplasms

Lip Neoplasms

Otorhinolaryngologic Neoplasms

Laryngeal Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Carboplatin

Diphenhydramine

Promethazine

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.

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.

Biospecimen Collection

Chest Radiography

Computed Tomography

Image Guided Radiation Therapy

Intensity-Modulated Radiation Therapy

Magnetic Resonance Imaging

Positron Emission Tomography

Heath D Skinner

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.

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:

I. 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.

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

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.

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.

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.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Complement C3

Complement C3d

Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant.

Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).

Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week

intensity-modulated radiation therapy (IMRT)

US Medical Information

Communication Center

Ragisha Gopalakrishnan

Ammar W Sukari

Rafi Kabarriti

Jessica Geiger

Ryan A Vaca

Marika Rasschaert

Michael Saerens

Frederic Forget

Willem Lybaert

Aron Popovtzer

Young Jin Choi

Keun-Wook Lee

Ji-Hyun Park

Hye Ryun Kim

Jung Hoon Kim

Jordi Rubio

Javier Serrano Andreu

Jaime Rubio Perez

Maria Jose Flor Oncala

Hui-Ching Wang

Ching-Yun Hsieh

Huai Cheng Huang

Muh-Hwa Yang

Medical Responsible

The purpose of this study is to evaluate the tolerability and safety of Xevinapant when added to weekly cisplatin-based concurrent chemoradiotherapy (CRT) in the treatment of participants with unresectable locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy.

Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)

A Single Arm, Open Label, Phase 1b Study of Xevinapant in Combination With Weekly Cisplatin and Intensity-modulated Radiotherapy to Assess Safety and Tolerability in Participants With LA SCCHN, Suitable for Definitive Chemoradiotherapy (HyperlynX)

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

LRC is defined as the time from date of the first treatment until date of the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes.

EMD Serono Research & Development Institute, Inc.

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Participants assigned to this cohort will receive xevinapant 50 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT).

An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Participants assigned to this cohort will receive xevinapant 100 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT).

An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Participants assigned to this cohort will receive xevinapant 150 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT).

An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Participants assigned to this cohort will receive xevinapant 200 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT).

An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Participants assigned to this cohort will receive xevinapant at the dose found during escalation phase of study for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT).

An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Given orally during study treatment on days 1-14 of a 21-day treatment cycles. It will be given continuously during treatment with carboplatin, paclitaxel, and radiation (chemoRT). After completely of the chemoRT dosing, an additional 3 cycles of Xevinapant along will be given.

Radiation will be given together with paclitaxel and carboplatin for 7 weeks.

Radiation Therapy

Clinical Trials Intake

Clinical Trial Intake

Ari Rosenberg, ND

The goal of this clinical trial is to determine the best safe dose of xevinapant that can be given in combination with chemotherapy and radiation in patients with head and neck cancer. Up to 4 doses of xevinapant will be tested in the dose escalation portion of the study. After the best safe dose is found during escalation, an additional group of participants will be enrolled at that dose to learn more about the treatment combination (dose expansion).

The main question\[s\] it aims to answer are:

* what is the maximum safe dose that can be given
* what dose should be used in subsequent (phase 2) trials

Participants will receive xevinapant in combination with paclitaxel and carboplatin chemotherapy and radiation. Treatment will be given in 3-week cycles for 3 cycles.

Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer

A Phase I Study of Xevinapant With Radiation and Concurrent Carboplatin and Paclitaxel in Patients Ineligible for Cisplatin With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Time from registration to the date of first documented disease progression based on RECIST v1.1, clinical progression, or death due to any cause, whichever occurs first.

Time between the date of registration and the date of death.

Time from registration to the date of first documented disease progression based on RECIST v1.1 in the head and neck.

Time from registration to the date of first documented disease progression based on RECIST v1.1 below the clavicles.

Complete or partial response per RECIST v1.1 criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Comparing RT With Cetuximab + Xevinapant to RT With Cetuximab-placebo in Patients With Head and Neck Cancer	NCT05930938	Squamous Cell C...	Xevinapant Placebo cetuximab IMRT	18 Years - 79 Years	Groupe Oncologie Radiotherapie Tete et Cou
Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma	NCT05724602	Locally Advance...	Xevinapant Placebo	70 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer	NCT06084845	Head and Neck S... Hypopharyngeal ... Laryngeal Squam... Oral Cavity Squ... Oropharyngeal S... Stage III Cutan... Stage III Hypop... Stage III Laryn... Stage III Lip a... Stage III Oroph... Stage IV Cutane... Stage IV Hypoph... Stage IV Laryng... Stage IV Lip an... Stage IV Oropha...	Biospecimen Col... Carboplatin Chest Radiograp... Cisplatin Computed Tomogr... Image Guided Ra... Intensity-Modul... Magnetic Resona... Positron Emissi... Xevinapant	18 Years -	Eastern Cooperative Oncology Group
Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)	NCT06056310	Head and Neck C...	Xevinapant Cisplatin intensity-modul...	18 Years -	EMD Serono
Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer	NCT06110195	Head and Neck C... Head and Neck N... Squamous Cell C...	Xevinapant Carboplatin Paclitaxel Radiation Thera...	18 Years -	University of Chicago
Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer	NCT06110195	Head and Neck C... Head and Neck N... Squamous Cell C...	Xevinapant Carboplatin Paclitaxel Radiation Thera...	18 Years -	University of Chicago
Study Comparing RT With Cetuximab + Xevinapant to RT With Cetuximab-placebo in Patients With Head and Neck Cancer	NCT05930938	Squamous Cell C...	Xevinapant Placebo cetuximab IMRT	18 Years - 79 Years	Groupe Oncologie Radiotherapie Tete et Cou
Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)	NCT06056310	Head and Neck C...	Xevinapant Cisplatin intensity-modul...	18 Years -	EMD Serono

Spots Global Cancer Trial Database for xevinapant

Every month we try and update this database with for xevinapant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for xevinapant

Every month we try and update this database with for xevinapant cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for xevinapant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.