NCT03508726

High Dose Ascorbate With Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas

Phase 1b/2 Neoadjuvant High Dose Ascorbate With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk and Retroperitoneum

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Mohammed Milhem · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm open-label phase Ib/II clinical study assessing the efficacy of concurrent high dose ascorbate in combination with radiotherapy in patients with locally advanced, resectable, high grade sarcomas.

Detailed description

Phase Ib: The phase Ib portion of this study is to ensure the safety and tolerability of high dose ascorbate in combination with external beam radiation therapy (EBRT) as assessed by incidence of dose-limiting toxicities (DLT). EBRT will be given at the standard dose for resectable soft tissue sarcomas according to the NCCN sarcoma guidelines.2 Patients will receive 50 Gy over 5 weeks, during which time they will be receiving three times a week IV high dose ascorbate. IV ascorbate infusions will be continued until the end of radiation therapy. Surgery will be performed 4-6 weeks from the end of radiation to allow for adequate tissue healing and resolution of acute toxicities. Phase 2: The phase 2 part of the study will provide an estimate of the relative treatment effect of pharmacological ascorbate in combination with preoperative EBRT in subjects with locally advanced, resectable, extremity, trunk or retroperitoneal high grade sarcomas, as measured by pathological response rates. As above, patients will receive the first dose of pharmacological ascorbate intravenously on day 1 of week 1 provided no reactions are seen to the test dose. This will be followed by 3 times a week dosing at Dose 0 until completion of EBRT. Standard doses of radiation for resectable soft tissue sarcomas according to the NCCN sarcoma guidelines will be administered.2 Patients will receive preoperative radiation at a dose of 50 Gy over 5 weeks starting on week 1 day 1. Subjects will be followed either by clinic visit or phone contact every 12 weeks for approximately 24 months after the end of the treatment phase, at which time the initial survival data and disease recurrence will be assessed.

Conditions

• Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Ascorbate	Phase 1 dose escalation: 75gm IV three times a week Phase II portion: 75gm IV three times a week if no dose limiting toxicities are experienced in the Phase I portion. Otherwise, ascorbate dose will be deescalated to 62.5 gm IV

Timeline

• Start date: 2019-06-27
• Primary completion: 2022-06-03
• Completion: 2024-06-02
• First posted: 2018-04-26
• Last updated: 2024-06-27
• Results posted: 2023-06-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study