The Phase I Results of a Phase 1/2 Trial for Patients With Newly Diagnosed Anal Cancer Treated With Concurrent Radiation Therapy, 5-Fluorouracil, Mitomycin and BMX-001.

Purpose/Objective(s) Radiation therapy with concurrent 5-fluorouracil and mitomycin (MMC) (CRT) for patients with locally advanced anal squamous cell carcinoma (ASCC) results in long-term disease-free survival and sphincter preservation, but often with significant toxicity. RTOG trials showed 43-87% ≥ grade (G) 3 acute toxicity. We hypothesize that BMX-001, a scavenger of O2, will decrease CRT-associated toxicity without compromising the survival outcome. The objectives of this phase I trial were to determine the maximum tolerated (MTD) BMX-001 primarily, and secondarily evaluate outcomes. Materials/Methods Eleven eligible stage II-III and pathologic confirmed ASCC patients received standard CRT. BMX-001 was given by sub-cutaneous injection, twice a week during CRT. Loading/maintenance dose escalation was as follows: 1) 7 and 3.5 mg/subject x 3; 2) 14 and 7 mg/subject x 3; 3) 28 and 14 mg/subject x 5. Endpoints (Toxicity and quality of life (QOL)) were assessed with CTCAE and EORTC QLQ-C30 questionnaires, respectively. Results All patients are free of disease with a median follow up of 17 (range 3-38) months. BMX-associated toxicity as follows: 6/11 G1 injection site erythema, 3/11 G2 sinus tachycardia, 1/11 G3 anxiety and hypertension and 1/11 G1 hypotension. All symptoms were relieved after hydrocortisone. No ≥ G 4 CRT-associated toxicities. G 1, 2 &3 CRT-associated toxicity during CRT was seen at skin (27/64/9%), gastrointestinal system (GI) (45/54/0%) and genitourinary system (GU) (64%/9/0%). All patients experienced anal pain during CRT (score 3-4/10: 44% and 5-9/10: 56%). At 1-month post-CRT, no G2 toxicity; G1 skin, GI and GU toxicity decreased to 0, 64 and 27%; Score 5-8/10 anal pain decreased to 27%. By 6 months, only 1 patient had anal pain scored 4/10 and 4 patients had G1 GI toxicity. Patients’ physical, role and social functioning scores decreased to the lowest point at week 6 of CRT and returned to pre-CRT level at 1-month post-CRT. Emotional and cognitive functioning did not decrease significantly during CRT. Conclusion BMX-001 MTD was not reached. A loading dose of 28 mg and a maintenance dose of 14 mg concurrent with CRT for anal squamous cell carcinoma is feasible and safe and is recommended for phase II trial. Concurrent CRT/BMX-001 was associated with decreased acute toxicities compared to RTOG data. Patients’ decreased QOL during CRT returns to pre-CRT status in 1 month. Clinical trial number NCT03386500.