A Randomized, Blinded, Placebo Controlled Phase 2 Trial of Concurrent Radiation Therapy and Cisplatin With and Without BMX-001 in Patients With Locally Advanced Head and Neck Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Mucositis Incidence
研究概览
简要总结
There are an estimated 65,000 newly diagnosed cases of head and neck cancer each year in the United States. The most common treatment for head and neck cancers is radiotherapy in combination with cisplatin chemotherapy. This treatment regimen is effective in killing the tumor; however, the normal tissues that line the mouth and throat can sustain severe injury from the radiation. Side-effects incurred during irradiation include: mucositis, xerostomia, swelling, trouble swallowing, pain, infections, cavities, hair loss and reddening of the skin. Some of these side effects can be so severe that patients require feeding tubes and management of severe pain can lead to the premature halt of radiotherapy. There are currently no effective radio-protectors used to ameliorate these severe side-effects.
BioMimetix has developed small molecular weight superoxide dismutase (SOD) mimetic, BMX-001, that is a very potent radio-protector of head and neck tissues. In our first clinical trial in a head and neck cancer patient cohort using this drug, we have early evidence that BMX-001 may protect against radiation-induced mucositis and xerostomia.
This will be a randomized, placebo-controlled Phase 2 clinical trial to study the effects of BMX-001 (14 mg/subject biw) + radiation therapy + cisplatin against placebo + radiation therapy + cisplatin in prevention of acute and chronic mucositis and xerostomia.
详细描述
This study will seek to confirm protection of normal tissues by assessing the incidence, severity and duration of mucositis in a randomized, placebo controlled, Phase 2 clinical trial of BMX-001 in combination with standard RT and chemotherapy in newly diagnosed head and neck cancer patients (162 subjects, 1:1 randomization study drug: placebo).
The study will also confirm protection of normal tissues by assessing the acute and chronic extent of xerostomia in the same trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Patients will be blinded as well as use of blinded assessors.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed (histologically or cytologically) diagnosis of squamous cell carcinoma of the oropharynx, larynx, hypopharynx, nasopharyngeal, or oral cavity with clinical or pathologic high-risk features who will be receiving radiation and concurrent cisplatin chemotherapy.
- •Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy depending on whether patients are receiving post-operative or definitive intent therapy respectively.
- •For patients undergoing curative intent resection, Patients must have undergone gross total surgical resection within 56 days prior to registration and beginning of therapy under the clinical trial.
- •General history and physical examination by a qualified head and neck cancer specialist and physician within 8 weeks prior to enrollment (including fiberoptic endoscopy).
- •Axial imaging of the neck and chest- CT, MRI and/or PET/CT is acceptable, within 8 weeks prior to date of consent.
- •Age ≥ 18 years.
- •Zubrod Performance Status 0-2 within 4 weeks prior to enrollment.
- •CBC/differential obtained within 2 weeks prior to starting the study drug with adequate bone marrow function
- •Adequate hepatic function
- •Adequate renal function defined as follows:
- •Patient must be willing and able to follow study procedures and instructions.
- •Patient must provide study-specific informed consent within 28 days prior to starting the study drug.
- •Negative pregnancy test for women of child-bearing potential within 48 hours prior to first dose of BMX-
- •Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until 12 months following the last study treatment.
排除标准
- •Distant metastasis
- •Hypertension
- •Grade ≥2 hypotension at screening
- •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
- •History of syncope within the last 6 months
- •Patients receiving, or unable to stop use of prohibited medications
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- •Women who are breast feeding are not eligible
- •Known hypersensitivity to compounds of similar chemical composition to BMX-001
- •Grade 3-4 electrolyte abnormalities (CTCAE v 5.0)
- •Prior unrelated malignancy requiring current active treatment with exceptions
- •Prior history of HNSCC receiving radiation or chemo-radiation.
- •Prior systemic chemotherapy for the study cancer (including neoadjuvant chemotherapy); note that prior chemotherapy for a different cancer is allowable.
- •Prior radiotherapy that would result in overlap of radiation treatment fields with planned treatment for study cancer.
- •A marked baseline prolongation of 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.
- •A history of additional risk factors for TdP
- •Severe, active co-morbidity as defined in the protocol
研究组 & 干预措施
A BMX-001
Patients will receive standard of care radiation therapy plus Cisplatin. BMX-001 will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: BMX-001 (Drug)
A BMX-001
Patients will receive standard of care radiation therapy plus Cisplatin. BMX-001 will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: Radiation Therapy (Radiation)
A BMX-001
Patients will receive standard of care radiation therapy plus Cisplatin. BMX-001 will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: Cisplatin (Drug)
B Placebo
Patients will receive standard of care radiation therapy plus Cisplatin. Placebo will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: Radiation Therapy (Radiation)
B Placebo
Patients will receive standard of care radiation therapy plus Cisplatin. Placebo will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: Cisplatin (Drug)
B Placebo
Patients will receive standard of care radiation therapy plus Cisplatin. Placebo will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Mucositis Incidence
时间窗: 12 weeks
The primary outcome measure used for each study subject is a dichotomous measure of whether they experienced severe oral mucositis (OM, defined as grade 3 or 4 according to WHO criteria) at any time between the first IMRT fraction until 30 days after the completion of RT. The primary analysis will thus test the difference in the proportion of subjects from each treatment group who experience severe OM.
次要结局
- Mucositis Severity(12 weeks)
- Xerostomia Incidence(1, 6, 12, and 24 months)
- Overall Survival(2 years)
- Disease Free Survival(2 years)
- Mucositis Duration(12 weeks)
- Radiation Dermatitis Duration(12 weeks)
- Saliva Production Measurements(1, 6, 12, and 24 months)