Trial of BMX-001 or Placebo in Head and Neck Cancer Patients

Phase 2

Withdrawn

• Conditions: Head and Neck Cancer
• Interventions: Drug: BMX-001; Radiation: Radiation Therapy; Other: Placebo; Drug: Cisplatin

• Registration Number: NCT04607642
• Lead Sponsor: BioMimetix JV, LLC

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-10-23
• Study First Submitted QC: 2020-10-23
• Study First Posted: 2020-10-29
• Study Start: 2021-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-04
• Last Update Posted: 2021-10-11
• Primary Completion: 2023-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. General history and physical examination by a qualified head and neck cancer specialist and physician within 8 weeks prior to enrollment (including fiberoptic endoscopy).
5. Axial imaging of the neck and chest- CT, MRI and/or PET/CT is acceptable, within 8 weeks prior to date of consent.
6. Age ≥ 18 years.
7. Zubrod Performance Status 0-2 within 4 weeks prior to enrollment.
8. CBC/differential obtained within 2 weeks prior to starting the study drug with adequate bone marrow function
9. Adequate hepatic function
10. Adequate renal function defined as follows:
11. Patient must be willing and able to follow study procedures and instructions.
12. Patient must provide study-specific informed consent within 28 days prior to starting the study drug.
13. Negative pregnancy test for women of child-bearing potential within 48 hours prior to first dose of BMX-001.
14. 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.

Exclusion Criteria

1. Distant metastasis
2. Hypertension
3. Grade ≥2 hypotension at screening
4. 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
5. History of syncope within the last 6 months
6. Patients receiving, or unable to stop use of prohibited medications
7. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
8. Women who are breast feeding are not eligible
9. Known hypersensitivity to compounds of similar chemical composition to BMX-001
10. Grade 3-4 electrolyte abnormalities (CTCAE v 5.0)
11. Prior unrelated malignancy requiring current active treatment with exceptions
12. Prior history of HNSCC receiving radiation or chemo-radiation.
13. Prior systemic chemotherapy for the study cancer (including neoadjuvant chemotherapy); note that prior chemotherapy for a different cancer is allowable.
14. Prior radiotherapy that would result in overlap of radiation treatment fields with planned treatment for study cancer.
15. 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.
16. A history of additional risk factors for TdP
17. Severe, active co-morbidity as defined in the protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A BMX-001	Radiation Therapy	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.
B Placebo	Radiation Therapy	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.
B Placebo	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.
A BMX-001	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.
A BMX-001	Cisplatin	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.
B Placebo	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Mucositis Incidence	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.

Secondary Outcome Measures

Name	Time	Method
Mucositis Severity	12 weeks	Days it takes for patients in each arm to develop severe oral mucositis.
Xerostomia Incidence	1, 6, 12, and 24 months	The dichotomous measure of whether the study subject had grade 2 (or greater) Xerostomia (as defined by CTCAE v 5.0). This will be assessed at 1, 6, 12, and 24 months after completion of RT.
Overall Survival	2 years	Overall survival (OS), defined as the interval (measured in days) from the date of randomization until the date of death from any cause.
Disease Free Survival	2 years	Disease-free survival (DFS), defined as the interval (measured in days) from the date of randomization until the date of CT scan showing tumor progression.
Mucositis Duration	12 weeks	The interval (measured in days) from the date of first determination of severe OM to the date of the first determination of not having severe OM, without a subsequent instance of severe OM.
Radiation Dermatitis Duration	12 weeks	The continuous endpoint of duration of radiation dermatitis, where duration is defined as the interval (measured in days) from the date of first determination of radiation dermatitis to the date of the first determination of not having radiation dermatitis, without a subsequent instance of radiation dermatitis. For any subject whose radiation dermatitis persists, the final date will be 30 days after the completion of RT.
Saliva Production Measurements	1, 6, 12, and 24 months	The continuous measure of saliva production (g/min), measured at baseline and 1, 6, 12, and 24 months after completion of RT. Both stimulated and unstimulated saliva production will be measured.