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
Purpose
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.
Conditions
- 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 Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
- Stage 0 Hypopharyngeal Carcinoma AJCC v8
- Stage 0 Nasopharyngeal Carcinoma AJCC v8
- Stage 0 Oropharyngeal (p16-Negative) Carcinoma AJCC v8
- Stage I Head and Neck Cutaneous Squamous Cell Carcinoma 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 Head and Neck Cutaneous Squamous Cell Carcinoma 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 Head and Neck Cutaneous Squamous Cell Carcinoma 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
- Stomatitis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 at least 1cc or 1% of the
subsite volume 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 or more subsites receiving >= 50 Gy must be
documented by the enrolling physician.
- 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 patients with T0/Tx/unknown primary disease.
- No definitive clinical or radiologic evidence of metastatic (M1) disease related to
current diagnosis.
- 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.
- Age >= 18.
- Zubrod performance status of 0-2.
- Potassium ≥ institutional lower limit of normal (LLN) and magnesium ≥ institutional
LLN. Oral or intravenous (IV) replacement therapy of potassium or magnesium is
permitted if parameters can be met after repletion.
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3.
- Platelets >= 100,000 cells/mm^3.
- Hemoglobin >= 9.0 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 steroid treatment as a component
of the anti-emetic regimen for cisplatin are eligible for the study. Treatment with
the antifungal medications, nystatin, fluconazole , miconazole and clotrimazole are
allowed.
- No prior induction chemotherapy treatment.
- No prior unrelated malignancy requiring current active treatment with the exception
of cervical carcinoma in situ, basal cell skin carcinoma, resected T1-2N0M0
differentiated thyroid cancers, Ta bladder cancers, or low risk prostate cancer.
- No clinically significant hearing impairment that precludes cisplatin, as per
physician assessment.
- No serious cardiovascular disease or cerebrovascular disease in the last 6 months
prior to study enrollment; defined as a cerebrovascular accident, myocardial
infarction, unstable angina, serious cardiac arrhythmia uncontrolled by medication
or with the potential to interfere with protocol treatment, or current New York
Heart Association (NYHA) grade II or greater congestive heart failure (CHF), or
admission within last 6 months for CHF exacerbation; (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 valvular heart disease.
- 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.
- No 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 known personal or family history of long QT Syndrome; no marked baseline
prolongation of QT/corrected QT (QTc) interval (i.e., ≥ 2 electrocardiograms [EKGs]
in prior 3 months of a QTc interval > 450 milliseconds (ms) for males and > 470 ms
for females using the specific/usual choice by clinical center for correction
factor.
- Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities must be
reversible to ≤ grade 1 with supplementation.
- No poorly controlled hypertension (systolic blood pressure [SBP] > 160 and/or
diastolic blood pressure [DBP] > 95) over 2 repeated measures within 30 days prior
to registration.
- No grade >= 2 oral mucositis per CTCAE version 5.0.
- No grade >= 2 hypotension per CTCAE v. 5.0.
- No medical necessity for anti-arrhythmics with significant risk of QTc prolongation
such as class I and class III anti-arrhythmics. These include but are not limited to
amiodarone, quinidine, dofetilide, sotalol, flecainide, and lidocaine.
- No medical necessity for medications listed as prohibited.
- For standard management of oral mucositis, clinicians may consult the
Multinational Association of Supportive Care in Cancer/International Society of
Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the Management of
Mucositis Secondary to Cancer Therapy. The only intervention against mucositis
that is supported by level I evidence is low-level laser therapy (LLLT). Honey
is rated at level II and benzydamine, which isn't available in the United
States (US), is rated at level III. There are no other positively rated
interventions.
- LLLT is prohibited in this study as its availability remains limited, it is not
Food and Drug Administration (FDA) approved in the US, and it is considered
investigational in many circumstances requiring enrollment in a dedicated
protocol who requirements could conflict with this one. Therefore, institutions
that use LLLT should only enroll patients who would not be eligible for (or do
not want) that intervention. Honey is not on the list of prohibited medications
for this study. Given the MASCC recommendation, benzydamine is allowed,
although there is lack of availability in the United States of America (USA).
The other listed prohibited medications are not recommended by MASCC and some
are potentially harmful, such as glutamine, which is associated with mortality
in patients receiving stem cell transplant.
- 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).
- Childbearing potential is defined as any person who has experienced menarche and who
has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or
who is not postmenopausal.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Double Blind. Fully blinded team members- Refers to individuals that have no access to view preparation of study drug. Study team members who are administering study drug (not preparing) will be included, however individuals that administer study drug should not perform efficacy assessments. Any investigator or sub-investigator involved in performing efficacy and safety assessments- These individuals should not be involved in preparation of the study drug and should avoid visual access during study drug administration when possible. Where possible, any other site staff member who does not have specific responsibilities that require access to IP (e.g., data entry assistant) should remain fully blinded.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Arm 1 (placebo) |
Patients receive cisplatin QW or Q3W and undergo image-guided intensity-modulated radiation therapy QD 5 days per week for 7 weeks per SOC. In addition to usual symptom management, patients receive placebo SC as early as 96 hours and no later than one hour prior to their first dose of radiation therapy, and as early as 96 hours and no later than 48 hours prior to first dose of cisplatin. Patients then receive placebo 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. |
|
|
Experimental Arm 2 (BMX-001) |
Patients receive cisplatin QW or Q3W and undergo image-guided intensity-modulated radiation therapy QD 5 days per week for 7 weeks per SOC. In addition to usual symptom management, patients receive BMX-001 SC as early as 96 hours and no later than one hour prior to their first dose of radiation therapy, and as early as 96 hours and no later than 48 hours prior to first dose of cisplatin. 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. |
|
Recruiting Locations
Gilbert, Arizona 85297
Peoria, Arizona 85381
Site Public Contact
623-773-2873
Phoenix, Arizona 85027
Scottsdale, Arizona 85258
Surprise, Arizona 85374
Tempe, Arizona 85284
Jonesboro, Arkansas 72401
Buena Park, California 90621
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714-522-0908
La Jolla, California 92093
Los Angeles, California 90033
Los Angeles, California 90033
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323-865-0451
Newport Beach, California 92663
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323-865-0451
San Diego, California 92103
Edwards, Colorado 81632
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970-569-7429
Washington D.C., District of Columbia 20037
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202-741-2210
N. Venice, Florida 34275
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Ruskin, Florida 33570
Sarasota, Florida 34232
Sarasota, Florida 34236
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Sarasota, Florida 34243
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Tampa, Florida 33607
Tampa, Florida 33612
Tampa, Florida 33612
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Wesley Chapel, Florida 33544
Bloomington, Illinois 61701
Bloomington, Illinois 61704
Canton, Illinois 61520
Chicago, Illinois 60611
Danville, Illinois 61832
DeKalb, Illinois 60115
Effingham, Illinois 62401
Eureka, Illinois 61530
Galesburg, Illinois 61401
Geneva, Illinois 60134
Kewanee, Illinois 61443
Macomb, Illinois 61455
Mattoon, Illinois 61938
Orland Park, Illinois 60462
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peoria, Illinois 61637
Peru, Illinois 61354
Princeton, Illinois 61356
Urbana, Illinois 61801
Warrenville, Illinois 60555
Washington, Illinois 61571
Ames, Iowa 50010
Ankeny, Iowa 50023
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515-241-3305
Cedar Rapids, Iowa 52403
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319-365-4673
Cedar Rapids, Iowa 52403
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Clive, Iowa 50325
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Des Moines, Iowa 50309
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Des Moines, Iowa 50309
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Iowa City, Iowa 52242
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Waukee, Iowa 50263
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Kansas City, Kansas 66160
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Westwood, Kansas 66205
Elizabethtown, Kentucky 42701
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270-706-5470
Baltimore, Maryland 21204
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443-849-3706
Boston, Massachusetts 02118
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Bay City, Michigan 48706
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Port Huron, Michigan 48060
Duluth, Minnesota 55805
Columbus, Mississippi 39705
Grenada, Mississippi 38901
New Albany, Mississippi 38652
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Cape Girardeau, Missouri 63703
Osage Beach, Missouri 65065
Reno, Nevada 89502
Lebanon, New Hampshire 03756
Albuquerque, New Mexico 87106
The Bronx, New York 10461
The Bronx, New York 10467
Albemarle, North Carolina 28002
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Charlotte, North Carolina 28203
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Charlotte, North Carolina 28210
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Charlotte, North Carolina 28262
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Concord, North Carolina 28025
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Durham, North Carolina 27710
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Gastonia, North Carolina 28054
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High Point, North Carolina 27262
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Monroe, North Carolina 28112
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Shelby, North Carolina 28150
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Winston-Salem, North Carolina 27157
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Akron, Ohio 44304
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Cincinnati, Ohio 45219
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West Chester, Ohio 45069
Oklahoma City, Oklahoma 73104
Chambersburg, Pennsylvania 17201
Ephrata, Pennsylvania 17522
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Erie, Pennsylvania 16505
Farrell, Pennsylvania 16121
Gettysburg, Pennsylvania 17325
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Mechanicsburg, Pennsylvania 17050
Monroeville, Pennsylvania 15146
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New Castle, Pennsylvania 16105
Pittsburgh, Pennsylvania 15215
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Pittsburgh, Pennsylvania 15232
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Collierville, Tennessee 38017
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Richmond, Virginia 23235
Richmond, Virginia 23298
Antigo, Wisconsin 54409
Ashland, Wisconsin 54806
Menomonee Falls, Wisconsin 53051
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262-257-5100
Milwaukee, Wisconsin 53226
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Milwaukee, Wisconsin 53295
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Mukwonago, Wisconsin 53149
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Oconomowoc, Wisconsin 53066
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Rhinelander, Wisconsin 54501
Stevens Point, Wisconsin 54481
Waukesha, Wisconsin 53188
Wausau, Wisconsin 54401
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West Bend, Wisconsin 53095
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Wisconsin Rapids, Wisconsin 54494
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More Details
- Status
- Recruiting
- Sponsor
- NRG Oncology
Study Contact
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 compare the duration of SOM in the BMX-001 arm versus (vs.) placebo arm. II. To assess the difference between arms in the Oral Mucositis Weekly Questionnaire-Head and Neck (OMWQ-HN) change score from baseline to 4 weeks after the end of chemoradiation. III. To describe the incidence and severity of xerostomia and radiation dermatitis, as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, in both arms. IV. To compare the duration of radiation dermatitis in the BMX-001 arm vs. placebo arm. V. To describe toxicity, as measured by CTCAE v5.0 and Patient Reported Outcome (PRO)-CTCAE, in both arms. 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 and plasma for future translational research analyses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive cisplatin once weekly (QW) or once every 3 weeks (Q3W) and undergo image-guided intensity-modulated radiation therapy once daily (QD) 5 days per week for 7 weeks per standard of care (SOC). In addition to usual symptom management, patients receive placebo subcutaneously (SC) as early as 96 hours and no later than one hour prior to their first dose of radiation therapy, and as early as 96 hours and no later than 48 hours prior to first dose of cisplatin. 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 cisplatin QW or Q3W and undergo image-guided intensity-modulated radiation therapy QD 5 days per week for 7 weeks per SOC. In addition to usual symptom management, patients receive BMX-001 SC as early as 96 hours and no later than one hour prior to their first dose of radiation therapy, and as early as 96 hours and no later than 48 hours prior to first dose of cisplatin. 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.