High Dose Ascorbate With Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT03508726|
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : July 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Soft Tissue Sarcoma||Drug: Ascorbate||Phase 1 Phase 2|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b/2 Neoadjuvant High Dose Ascorbate With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk and Retroperitoneum|
|Actual Study Start Date :||June 27, 2019|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2022|
Experimental: Phase I dose escalation/Phase II portion
Phase 1 dose escalation:
Patients will receive radiation therapy over 5 weeks, during which time they will be receiving ascorbate infusions three times a week. Ascorbate infusions will be continued until the end of radiation therapy. Surgery will be performed 4-6 weeks from the end of radiation.
Phase II portion:
Patients will receive radiation therapy over 5 weeks, during which time they will be receiving intravenous (IV) ascorbate infusions three times a week. Ascorbate infusions will be continued until the end of radiation therapy. Surgery will be performed 4-6 weeks from the end of radiation.
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
- Incidence of dose limiting toxicities (DLTs) using CTCAE, Version 4.0 [ Time Frame: Start of treatment up to 4 weeks after the last ascorbate infusion ]To examine the toxicity related to the therapy by measuring the number attributed adverse event (definite, probable or possible) according to CTCAE version 4.0.
- Tumor response as assessed by pathological complete response rates (pCR) [ Time Frame: Start of treatment up to 6 weeks after the last ascorbate infusion ]For this study, pCR will be defined as ≥ 95% tumor necrosis following concurrent radiation therapy and ascorbate.
- Disease progression as measured by time to disease progression (TTP) [ Time Frame: Enrollment or start of treatment up to 2 years following end of treatment ]Time to disease progression (TTP) is defined as the time from enrollment until objective tumor progression including local and distant recurrences.
- Overall response rate as measured by RECIST 1.1 [ Time Frame: Enrollment or start of treatment up to 2 years following end of treatment ]Overall response rate (ORR) preoperative as measured by RECIST 1.1 or a later tool for monitoring disease progression.
- Overall survival estimated using the Kaplan-Meier Method [ Time Frame: Enrollment or start of treatment up to 2 years following end of treatment ]Overall survival (OS) rate data gathered through passive chart review, phone call or scheduled follow-up visit and estimated using the Kaplan-Meier Method.
- Skin toxicity [ Time Frame: Within two years following end of treatment ]Pathologist to grade radiation related skin toxicity overlying the tumor as compared to historical controls. Binomial exact tests will be utilized to identify differences in wound complication and Grade 3-4 dermatitis rates compared to historical controls.
- Labile iron [ Time Frame: Within two years following end of treatment ]To measure labile iron using T2* imaging sequence on MRI pre and post ascorbate treatments and compare with serum iron measurements
- Evaluate diffusion weighted imaging sequences [ Time Frame: Within two years following end of treatment ]To evaluate diffusion weighted imaging sequences on MRI in pre and post treatment tumors and correlate it with necrosis and survival
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03508726
|Contact: Varun Monga, MBBSfirstname.lastname@example.org|
|United States, Iowa|
|University of Iowa Hospitals and Clinics||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Varun Monga, MBBS|
|Principal Investigator:||Varun Monga, MBBS||University of Iowa|