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A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer.

Publication ,  Conference
Brizel, DM; Mowery, YM; Zhen, W; Chan, J; Macleod, D; Yom, SS
Published in: International journal of radiation oncology, biology, physics
November 2021

Prevention/mitigation of oral mucositis (OM) and xerostomia are challenges to the use of chemoradiation (CRT) for advanced head and neck squamous ca (HNSCC). MnTnBuOE-2-PyP5+(BMX-001) is a lipophilic manganese metalloporphyrin superoxide dismutase mimic that protects against radiation and chemotherapy induced OM in orthotopic animal tumor models. This study objective was to determine the toxicity profile of BMX-001 given during CRT for locally advanced HNSCC and to measure the incidence of severe (CTCAE v 4.03 grade 3-4) OM and xerostomia.Multi-center prospective phase 1-2 open label trial for patients with AJCC 7 stage III/IVB HNSCC undergoing concurrent RT/cisplatin, curative (70 Gy) or post-op (60-66 Gy). BMX-001 was administered subcutaneously 2x/week during CRT with an initial loading dose given up to 4 days prior to the start of CRT. Two additional doses of BMX-001 were given in the first week post-CRT. A 3+3 design was used. BMX-001 dose levels were 1: 7 mg load/3.5 mg maintenance; 2: 14 mg load/ 7mg maintenance; 3: 28 mg load/ 14 mg maintenance. Level 3 was expanded to assess phase 2 endpoints. Co-primary endpoints: toxicity of BMX-001 and the incidence of severe (grade 3-4) OM. OM was evaluated 2x/week during CRT and then weekly for 4 additional weeks. Secondary endpoints: median duration and time to onset of grade 3-4 OM, grade ≥2 xerostomia 1- and 6-months post-CRT, and progression-free survival (PFS).A total of 29 patients (M:F = 25:4) were enrolled from 5/2017-12/2019. Primary sites: p16+ oropharynx 25 (86%), nasopharynx (1), hard palate (1), unknown primary (2). Median age: 62 yo (IQR:56-67). Dose levels were 1 (3); 2 (3); dose 3 (23). Median RT dose: 70 Gy (IQR 70-70). 79.3% of subjects received > 200mg/m2 of CDDP. All subjects on levels 1 and 2 received all BMX-001 as prescribed by protocol. Level 3, 19/23 (83%) received all doses of BMX-001. All patients had a grade 1 injection site reaction. There were 2 (7%) mild AEs related to QT interval prolongation and 3 serious adverse events (SAE) categorized as possibly related to BMX-001: hypotension, fever with pancytopenia, and hyponatremia. Other SAEs (n = 19) were judged to be expected due to the nature of the disease or treatment with CRT. Incidence of severe OM was 41% (median duration 25 days, IQR 25-47). Median time to onset of severe OM was 43 (IQR 34-52) days; 83.3% cases of severe OM resolved by 5 weeks post-CRT. Incidence of grade ≥ 2 xerostomia was 18%, 8%, and 9% at 1, 6, and 12 months respectively post-CRT. Mean unstimulated whole saliva production was 0.69 ml/min at baseline and 0.29 ml/min at 1 yr. Mean stimulated whole saliva production was 1.38 ml/min at baseline and 0.72ml/min at 1 yr. Median follow up was 20 mo. 1 yr PFS was 96.6%.CRT and 2x/week BMX-001 was safe in HNSCC at the highest dose tested. Promising rates of severe OM and xerostomia justify further investigation in HNSCC patients receiving CRT.

Duke Scholars

Published In

International journal of radiation oncology, biology, physics

DOI

EISSN

1879-355X

ISSN

0360-3016

Publication Date

November 2021

Volume

111

Issue

3S

Start / End Page

S145

Related Subject Headings

  • Oncology & Carcinogenesis
  • 5105 Medical and biological physics
  • 3407 Theoretical and computational chemistry
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
  • 0299 Other Physical Sciences
 

Citation

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Brizel, D. M., Mowery, Y. M., Zhen, W., Chan, J., Macleod, D., & Yom, S. S. (2021). A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer. In International journal of radiation oncology, biology, physics (Vol. 111, p. S145). https://doi.org/10.1016/j.ijrobp.2021.07.325
Brizel, D. M., Y. M. Mowery, W. Zhen, J. Chan, D. Macleod, and S. S. Yom. “A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer.” In International Journal of Radiation Oncology, Biology, Physics, 111:S145, 2021. https://doi.org/10.1016/j.ijrobp.2021.07.325.
Brizel DM, Mowery YM, Zhen W, Chan J, Macleod D, Yom SS. A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer. In: International journal of radiation oncology, biology, physics. 2021. p. S145.
Brizel, D. M., et al. “A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer.International Journal of Radiation Oncology, Biology, Physics, vol. 111, no. 3S, 2021, p. S145. Epmc, doi:10.1016/j.ijrobp.2021.07.325.
Brizel DM, Mowery YM, Zhen W, Chan J, Macleod D, Yom SS. A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer. International journal of radiation oncology, biology, physics. 2021. p. S145.
Journal cover image

Published In

International journal of radiation oncology, biology, physics

DOI

EISSN

1879-355X

ISSN

0360-3016

Publication Date

November 2021

Volume

111

Issue

3S

Start / End Page

S145

Related Subject Headings

  • Oncology & Carcinogenesis
  • 5105 Medical and biological physics
  • 3407 Theoretical and computational chemistry
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
  • 0299 Other Physical Sciences