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

NCT04607642 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: BMX-HN-201
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Head and Neck Cancer

Keywords

head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Mucositis Incidence

  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.

  12 weeks

Secondary Outcomes (7)

• Mucositis Duration

  12 weeks

• Mucositis Severity

  12 weeks

• Xerostomia Incidence

  1, 6, 12, and 24 months

• Saliva Production Measurements

  1, 6, 12, and 24 months

• Radiation Dermatitis Duration

  12 weeks

Study Arms (2)

A BMX-001

EXPERIMENTAL

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.

Drug: BMX-001; Radiation: Radiation Therapy; Drug: Cisplatin

B Placebo

PLACEBO COMPARATOR

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.

Radiation: Radiation Therapy; Drug: Cisplatin; Other: Placebo

Interventions

BMX-001 DRUG

BMX-001 consists of a porphyrin ring with pyridyl groups attached at each of the four methane bridge carbons. The nitrogen in the pyridyl ring is at the 2 position and has a side chain consisting of six carbons with an ether linkage. A manganese atom is chelated into the porphyrin ring and is the active center of the molecule. This molecule is an enzymatic scavenger of free radical species operating at close to diffusion-limited rates.

Also known as: manganese butoxyethyl pyridyl porphyrin, MnTnBuOE-2-PyP5+

A BMX-001

Radiation Therapy RADIATION

Treatment plan should include a continuous course of treatment delivered as single daily fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy. Planned radiation treatment volumes must include at least two oral mucosal sub-sites (buccal mucosa, retromolar trigone, floor of mouth, tongue, soft palate, hard palate) with a portion of each site receiving at least 50 Gy.

A BMX-001; B Placebo

Cisplatin DRUG

Cisplatin is an IV chemotherapeutic agent approved to treat head and neck cancers. Cisplatin will be administered per institution's standard of care practice. Common standard of care practice includes dosing cisplatin at 100mg/m2 IV q21 days starting on Day 1 of RT for 2-3 doses or dosing cisplatin at 40 mg/m2 IV each week of RT for 6-7 total doses. Cisplatin will be infused per institutional guidelines.

A BMX-001; B Placebo

Placebo OTHER

The placebo to be used in this study is 0.9% Sodium Chloride Injection, USP.

B Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-001.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMimetix JV, LLC: lead
• Duke University: collaborator
• University of California, San Francisco: collaborator

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin; Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• James Crapo, MD

  BioMimetix JV, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients will be blinded as well as use of blinded assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: October 29, 2020
• Study Start: July 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2025
• Last Updated: October 11, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share