A Trial of Concurrent Radiation Therapy, Cisplatin, and BMX-001 in Locally Advanced Head and Neck Cancer

NCT02990468 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BMX-HN-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1 / Phase 2 study of newly diagnosed patients with biopsy-proven head and neck cancer (squamous cell carcinoma) who are undergoing standard radiation therapy and treatment with cisplatin. BMX-001 added to radiation therapy and cisplatin is expected to reduce radiation-induced mucositis and xerostomia and also has the potential to benefit the survival of head and neck cancer patients. In Phase 1, safety and tolerability of BMX-001 will be assessed using a Continual Reassessment Method (CRM) and a maximum tolerated dose (MTD) will be determined. BMX-001 will be given subcutaneously first with a loading dose zero to four days prior to the start of chemoradiation and followed by twice a week doses at one-half of the loading dose for the duration of radiation therapy plus two weeks. In Phase 2 both safety and efficacy of BMX-001 will be evaluated. Impact on mucositis and xerostomia will also be assessed. A maximum of 48 patients will be enrolled to the MTD dose determined in Phase 1 to confirm the MTD. The investigators hypothesize that BMX-001 when added to standard radiation therapy and cisplatin will be safe at pharmacologically relevant doses in patients with newly diagnosed head and neck cancer. The investigators also hypothesize that in Phase 2 of this study the addition of BMX-001 will reduce the severity of radiation-induced mucositis and xerostomia in patients receiving head and neck radiation therapy.

Conditions

Head and Neck Cancer

Keywords

Mucositis; Xerostomia

Outcome Measures

Primary Outcomes (2)

• Assess the Safety of the Study Drug by Calculating the Proportion of Patients Who Experience Grade 4 or 5 Study Drug Related Adverse Events, as Assessed by CTCAE v 4.03.

  This outcome is to confirm the safety and tolerability of escalating doses of BMX-001 in conjunction with RT and concurrent cisplatin in a cohort of newly diagnosed patients with locally advanced head and neck cancers. Each dose will be reported separately.

  1 year

• Incidence Radiation-induced Mucositis by Clinician Scoring

  Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Higher scores are indicative of worse symptoms. Grade 0-5. We are reporting the incidence of the patients that had mucositis grade 1-5.

  6 months

Secondary Outcomes (5)

• Incidence of Radiation-induced Xerostomia by Stimulated Saliva Production

  6 months

• Incidence of Radiation-induced Xerostomia by Unstimulated Saliva Production

  6 months

• Incidence of Radiation-induced Xerostomia by Clinician Scoring

  6 months

• Duration of Radiation-induced Mucositis

  6 month 6 months

• To Examine the Impact on Radiation Dermatitis When Adding BMX-001 to Treatment

  30 days

Study Arms (1)

Radiation Therapy, Cisplatin and BMX-001

EXPERIMENTAL

In Phase 1, safety and tolerability of BMX-001 will be assessed using a Continual Reassessment Method and a maximum tolerated dose (MTD) will be determined using a single arm design. In Phase 2, the severity of radiation-induced mucositis and xerostomia will be assessed using a single arm design.

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

Interventions

BMX-001 DRUG

Subcutaneous injection.

Radiation Therapy, Cisplatin and BMX-001

Radiation Therapy RADIATION

Patients will receive standard dose intensity modulated radiation therapy (IMRT).

Radiation Therapy, Cisplatin and BMX-001

Cisplatin DRUG

Cisplatin will be administered per institution's standard of care practice.

Radiation Therapy, Cisplatin and BMX-001

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or oral cavity with clinical or pathologic high-risk features for whom cisplatin and radiation would be considered appropriate care.
• 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 considered post-operative high risk or unresectable/organ preservation high risk. Planned radiation treatment fields must include at least two oral sites buccal mucosa, retromolar trigone, floor of mouth, oral tongue, soft palate, hard palate) with a portion of each site receiving a minimum total of 50 Gy.
• Patients who are to undergo definitive chemoradiation must have clinically or radiographically evident measurable disease at the primary site and/or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted.
• Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions. Fine needle aspirations of the neck that are positive for squamous cell carcinoma are sufficient for diagnosis pending pathology review at participating institutions.
• For patients undergoing curative intent resection the following criteria are required:
• Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma
• Patients must have undergone gross total surgical resection within 42 days prior to registration and beginning of therapy under the clinical trial. Note: Patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection.
• Clinical or pathologic stage Stage III-IVb per the American Joint Committee on Cancer (AJCC), 7th edition.
• General history and physical examination by a radiation oncologist and medical oncologist within 4 weeks prior to enrollment.
• Examination by an ear/nose/throat (ENT) or head and neck surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to enrollment.
• Zubrod Performance Status 0-2 within 4 weeks prior to enrollment
• Complete blood count (CBC)/differential obtained within 7 days prior to starting the study drug with adequate bone marrow function, defined as follows:
• Hemoglobin ≥ 9.0 g/dl;
• Platelets ≥ 100,000 cells/mm3;
• Absolute neutrophil count (ANC) \> 1,500 cell/mm3.

You may not qualify if:

• Stage I or II; T1N1 and T2N1 stage III presentations per AJCC 7th edition
• Distant metastasis
• Hypertension requiring 3 or more anti-hypertensive medications to control
• Grade ≥2 hypotension at screening
• Requirement for 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 at least 1 week prior to receiving the first dose of BMX-001, medications listed in Section 12.2 of the protocol are not eligible.
• Women who are breast feeding are not eligible
• Prior allergic reaction to cisplatin
• Known hypersensitivity to compounds of similar chemical composition to BMX-001
• Grade 3-4 electrolyte abnormalities (CTCAE v 4.03) except sodium, which must be ≥126 mmol/L.
• Prior unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ, basal cell carcinoma of the skin, resected T1-2N0M0 differentiated thyroid cancers, invasive cancers with a 3-year disease-free interval, Ta bladder cancers, or low and favorable intermediate risk prostate cancer.
• 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.

Sponsors & Collaborators

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

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Florida- Gainesville

Gainesville, Florida, 32609, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Mucositis; Xerostomia

Interventions

Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This was a dose escalation study with all subjects receiving the intervention. There was no control arm for comparison. This will be addressed in a future clinical trial. This study design was effective for a safety, dose-escalation study.

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: BioMimetix JV LLC

contact@bmxpharma.com

303-862-7268

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 13, 2016
• Study Start: April 19, 2017
• Primary Completion: February 21, 2020
• Study Completion: March 31, 2022
• Last Updated: March 15, 2023
• Results First Posted: March 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)