Trial Title:
Testing the Addition of the Drug BMX-001, a Radioprotector, or a Placebo to the Usual Chemoradiation Therapy for Patients With Head and Neck Cancer
NCT ID:
NCT06532279
Condition:
Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Head and Neck Squamous Cell Carcinoma
Hypopharyngeal Squamous Cell Carcinoma
Laryngeal Squamous Cell Carcinoma
Nasopharyngeal Squamous Cell Carcinoma
Oral Cavity Squamous Cell Carcinoma
Oropharyngeal Squamous Cell Carcinoma
Stage 0 Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage 0 Hypopharyngeal Carcinoma AJCC v8
Stage 0 Nasopharyngeal Carcinoma AJCC v8
Stage 0 Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage I Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage I Hypopharyngeal Carcinoma AJCC v8
Stage I Laryngeal Cancer AJCC v8
Stage I Lip and Oral Cavity Cancer AJCC v8
Stage I Nasopharyngeal Carcinoma AJCC v8
Stage I Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage II Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage II Hypopharyngeal Carcinoma AJCC v8
Stage II Laryngeal Cancer AJCC v8
Stage II Lip and Oral Cavity Cancer AJCC v8
Stage II Nasopharyngeal Carcinoma AJCC v8
Stage II Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage III Hypopharyngeal Carcinoma AJCC v8
Stage III Laryngeal Cancer AJCC v8
Stage III Lip and Oral Cavity Cancer AJCC v8
Stage III Nasopharyngeal Carcinoma AJCC v8
Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage IVA Hypopharyngeal Carcinoma AJCC v8
Stage IVA Laryngeal Cancer AJCC v8
Stage IVA Lip and Oral Cavity Cancer AJCC v8
Stage IVA Nasopharyngeal Carcinoma AJCC v8
Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage IVB Hypopharyngeal Carcinoma AJCC v8
Stage IVB Laryngeal Cancer AJCC v8
Stage IVB Lip and Oral Cavity Cancer AJCC v8
Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Carcinoma
Squamous Cell Carcinoma of Head and Neck
Laryngeal Neoplasms
Mouth Neoplasms
Oropharyngeal Neoplasms
Lip Neoplasms
Manganese
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Double (Participant, Investigator)
Masking description:
Double Blind
Intervention:
Intervention type:
Other
Intervention name:
Best Practice
Description:
Receive usual symptom management
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
standard of care
Other name:
standard therapy
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood, serum, and/or plasma samples
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Given cisplatin
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
Abiplatin
Other name:
Blastolem
Other name:
Briplatin
Other name:
CDDP
Other name:
Cis-diammine-dichloroplatinum
Other name:
Cis-diamminedichloridoplatinum
Other name:
Cis-diamminedichloro Platinum (II)
Other name:
Cis-diamminedichloroplatinum
Other name:
Cis-dichloroammine Platinum (II)
Other name:
Cis-platinous Diamine Dichloride
Other name:
Cis-platinum
Other name:
Cis-platinum II
Other name:
Cis-platinum II Diamine Dichloride
Other name:
Cismaplat
Other name:
Cisplatina
Other name:
Cisplatinum
Other name:
Cisplatyl
Other name:
Citoplatino
Other name:
Citosin
Other name:
Cysplatyna
Other name:
DDP
Other name:
Lederplatin
Other name:
Metaplatin
Other name:
Neoplatin
Other name:
Peyrone's Chloride
Other name:
Peyrone's Salt
Other name:
Placis
Other name:
Plastistil
Other name:
Platamine
Other name:
Platiblastin
Other name:
Platiblastin-S
Other name:
Platinex
Other name:
Platinol
Other name:
Platinol- AQ
Other name:
Platinol-AQ
Other name:
Platinol-AQ VHA Plus
Other name:
Platinoxan
Other name:
Platinum
Other name:
Platinum Diamminodichloride
Other name:
Platiran
Other name:
Platistin
Other name:
Platosin
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Radiation
Intervention name:
Image Guided Radiation Therapy
Description:
Undergo image-guided radiation therapy
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
IGRT
Other name:
image-guided radiation therapy
Other name:
Image-Guided Radiotherapy
Intervention type:
Radiation
Intervention name:
Intensity-Modulated Radiation Therapy
Description:
Undergo intensity-modulated radiation therapy
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
IMRT
Other name:
Intensity modulated radiation therapy (procedure)
Other name:
Intensity Modulated RT
Other name:
Intensity-Modulated Radiotherapy
Other name:
Radiation, Intensity-Modulated Radiotherapy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
MnSOD Mimetic BMX-001
Description:
Given SC
Arm group label:
Arm 2 (BMX-001)
Other name:
BMX-001
Other name:
Manganese (III) ortho N-Butoxyethylpyridylporphyrin
Other name:
Manganese Butoxyethyl Pyridyl Porphyrin
Other name:
Mitochondrial Manganese Superoxide Dismutatse Mimetic BMX-001
Other name:
Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
Other name:
MnTnBuOE-3-PyP 5+
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given SC
Arm group label:
Arm 1 (placebo)
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm 1 (placebo)
Arm group label:
Arm 2 (BMX-001)
Summary:
This phase II trial compares the effectiveness of adding BMX-001 to usual symptom
management versus usual symptom management alone for reducing oral mucositis in patients
who are receiving chemoradiation for head and neck cancer. Oral mucositis (inflammation
and mouth sores) is a common side effect of chemoradiation that can cause pain and
difficulty swallowing. Usual management of these side effects typically consists of using
mouth rinses and pain medications during treatment and for several weeks after completion
of treatment. BMX-001 neutralizes harmful substances in the body, preventing damage to
macromolecules such as DNA and minimizes free radical-related toxicity in normal tissues.
Adding BMX-001 to usual symptom management may be more effective than usual symptom
management alone at reducing oral mucositis in patients receiving chemoradiation for head
and neck cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare the incidence of severe oral mucositis (SOM) between manganese superoxide
dismutase (MnSOD) mimetic BMX-001 (BMX-001) and placebo, defined as >= grade 3 per World
Health Organization (WHO) criteria from the start of radiation through 4 weeks after
completion of study treatment, with additional assessments at 6, 8 and 12 weeks after
completion of study treatment.
SECONDARY OBJECTIVES:
I. To determine if the duration of SOM is shorter in the BMX-001 arm versus (vs.) placebo
arm.
II. To assess the difference in Oral Mucositis Weekly Questionnaire-Head and Neck
(OMWQ-HN) change score from baseline to 4 weeks after the end of radiation.
III. Incidence and severity of xerostomia and radiation dermatitis, as measured by Common
Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
IV. To determine if the duration of radiation dermatitis is shorter in the BMX-001 arm
vs. placebo arm.
V. Toxicity, as measured by CTCAE v5.0 and Patient Reported Outcome (PRO)-CTCAE.
EXPLORATORY OBJECTIVES:
I. To assess the between arm difference in progression-free survival (PFS). II. To assess
the between arm difference in overall survival (OS). III. Data demonstrating improvement
in pain, as measured by reduction in narcotic use between BMX-001 versus usual care.
IV. Collect serum, plasma and imaging studies for future translational research analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive weekly cisplatin and undergo image-guided intensity-modulated
radiation therapy per standard of care (SOC). In addition to usual symptom management,
patients receive placebo subcutaneously (SC) as early as 4 days and no later than one
hour prior to their first dose of radiation therapy. Patients then receive placebo SC
twice a week (BIW) for 8 weeks (16 doses). Patients also undergo computed tomography (CT)
and/or magnetic resonance imaging (MRI) on study and may optionally undergo collection of
blood, serum, and/or plasma throughout the study.
ARM 2: Patients receive weekly cisplatin and undergo image-guided intensity-modulated
radiation therapy per SOC. In addition to usual symptom management, patients receive
BMX-001 SC as early as 4 days and no later than one hour prior to their first dose of
radiation therapy. Patients then receive BMX-001 SC BIW for 8 weeks (16 doses). Patients
also undergo CT and/or MRI on study and may optionally undergo collection of blood,
serum, and/or plasma throughout the study.
After completion of study treatment, patients are followed up at 1, 2, 3, 6, 12, and 24
months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must be planned to receive radiation and concurrent cisplatin chemotherapy
as definitive therapy. Patients planned to receive concurrent cisplatin and
radiation therapy in the adjuvant setting are not eligible.
- At least two subsites (buccal mucosa, lips, retromolar trigone, floor of mouth, oral
tongue, tonsil, soft palate, or hard palate) must have a portion receiving >= 50 Gy.
In cases of uncertainty, the enrolling clinician can ensure coverage by inspecting
the 50 Gy isodose line and using the table describing the anatomic boundaries of the
individual subsites contained within the extended cavity contour. The two subsites
receiving >= 50 Gy must be documented by the enrolling physician and will be
reviewed centrally to confirm eligibility.
- Pathologically confirmed (histologically or cytologically) squamous cell carcinoma
of the oropharynx, larynx, hypopharynx, nasopharynx, or oral cavity.
- P16 and/or human papillomavirus (HPV) status (via polymerase chain reaction [PCR] or
in situ hybridization [ISH]) must be documented for patients with oropharynx cancer.
- No definitive clinical or radiologic evidence of metastatic (M1) disease related to
current diagnosis.
- No prior unrelated malignancy requiring current active treatment with the exception
of cervical carcinoma in situ, basal cell carcinoma, resected T1-2N0M0
differentiated thyroid cancers, Ta bladder cancers, or low risk prostate cancer.
- Able to receive intensity-modulated radiation therapy (IMRT) delivered as daily
fractions of 2.0 Gy once per weekday with a cumulative radiation dose of 70 Gy.
- Planned radiation treatment volumes must include at least two oral sub-sites
(defined as buccal mucosa, retromolar trigone, floor of mouth, oral tongue, tonsil,
soft palate, hard palate) with a portion each of the two subsites receiving >= 50
Gy. Clinical centers will document which subsites will receive >= 50 Gy.
- Age >= 18.
- Zubrod performance status of 0-2.
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3.
- Platelets >= 100,000 cells/mm^3.
- Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to
achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable).
- Adequate renal function defined as creatinine clearance (CrCL) > 50 mL/min by the
Cockcroft-Gault formula.
- Total bilirubin =< 2 x institutional upper limit of normal (ULN) (not applicable to
patients with known Gilbert's syndrome).
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<
3 x institutional ULN.
- No prior radiotherapy that would result in overlap of radiation treatment fields
with planned treatment for study cancer, e.g., breast cancer with irradiation of the
supraclavicular fossa/level 4 neck.
- No concurrent treatment with nitrates or other drugs that may, in the judgment of
the treating investigator, create a risk for a precipitous decrease in blood
pressure.
- No prior history of gross total excision of both primary and nodal disease; this
includes tonsillectomy, local excision of primary site, and nodal excision that
removes all clinically and radiographically evident disease. In other words, to
participate in this protocol, the patient must have clinically or radiographically
evident gross disease for which disease response can be assessed.
- No current treatment of adjuvant post-operative (op) chemoradiation.
- No systemic treatment with inducers or strong inhibitors of cytochrome P450 =< 4
days before registration. Note: Patients undergoing dexamethasone treatment are
eligible for the study.
- No significant hearing impairment as per physician assessment.
- No history of unstable angina requiring hospitalization in the last 6 months.
- No history of myocardial infarction within the last 6 months.
- New York Heart Association Functional Classification II or better (New York Heart
Association [NYHA] Functional Classification III/IV are not eligible) (Note:
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.).
- No cardiovascular disease or cerebrovascular disease, for example cerebrovascular
accidents or myocardial infarction =< 6 months prior to study enrollment, unstable
angina, New York Heart Association (NYHA) grade II or greater congestive heart
failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with the
potential to interfere with protocol treatment.
- No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent arterial thrombosis) within 6 months prior to enrollment.
- No history or evidence upon physical/neurological examination of central nervous
system disease (e.g., seizures) unrelated to cancer unless adequately controlled by
medication.
- Acute bacterial, viral, or fungal infection requiring intravenous antimicrobials
within 7 days of enrollment.
- No history of chronic obstructive pulmonary disease exacerbation or other
respiratory illness requiring hospitalization or precluding study therapy within 30
days of registration.
- No history of syncope within the last 6 months.
- No history of additional risk factors for Torsades de Pointes (e.g., congestive
heart failure, hypokalemia, known family history of long QT syndrome).
- No marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., repeated
demonstration of a QTc interval > 480 milliseconds [ms] using the specific/usual
choice by clinical center for correction factor).
- No feeding tube.
- No hypertension requiring >= 3 anti-hypertensive medications.
- No grade >= 2 oral mucositis per CTCAE version 5.0.
- No grade >= 2 hypotension per CTCAE v. 5.0.
- Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities must be
reversible with replacement.
- No medical necessity for medications listed as prohibited.
- No history of allergic reaction to the study agent(s), compounds of similar chemical
or biologic composition to the study agent (s) (or any of its excipients).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
October 30, 2024
Completion date:
September 15, 2026
Lead sponsor:
Agency:
NRG Oncology
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
NRG Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06532279
