Soft Tissue SarcomaPhase 1/2NCT03508726
High Dose Ascorbate With Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
A Phase 1/2 study testing Ascorbate in people with Soft Tissue Sarcoma, run by Mohammed Milhem at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Ascorbate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2019to 2 Jun 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject or subject's legally acceptable representative has provided informed consent.
- Histologically confirmed diagnosis of locally advanced soft tissue sarcoma of extremity, trunk or retroperitoneum that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate
- Including metastatic (stage IV) disease for which radiotherapy and surgical resection of the primary tumor are indicated.
- Patients with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
- Patients do not have histologic subtypes: GIST, Desmoid, Ewing sarcoma, bone sarcomas and Kaposi sarcoma.
- Age ≥18 years.
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- Patients with a history of non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
- ECOG performance status </=1.
- Tolerate one test dose (15g) of ascorbate.
- Patient must have measurable disease:
- Tumor size at least >/= 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible and indicated.
Who cannot join
- Inadequate organ function within 21 days of Day 1 of study as defined by:
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count (ANC) </= 1500 per mm3
- Platelet count </= 100,000 per mm3
- Total bilirubin >/= 1.5 × ULN. Subjects with direct bilirubin < ULN with total bilirubin levels > 1.5 X ULN will not be excluded.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN
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- Alkaline phosphatase > 2.5 × ULN
- PT (or INR) and PTT (or aPTT) >/= 1.5 × ULN
- Creatinine > 2.0 × ULN
- G6PD (glucose-6-phosphate dehydrogenase) deficiency.
- Prior history of symptomatic oxalate kidney stones within the last year.
- Prior radiation therapy in excess of 20 Gy to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
- Prior history of receiving pharmacological ascorbate.
- Patients actively receiving insulin therapy and needing daily fingerstick for glucose monitoring.
- Concurrent, clinically significant, active malignancies within two years of study enrollment.
- Female subjects who are pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment.
- Female subjects of childbearing potential or male subjects who are unwilling to use 2 highly effective methods of contraception during study treatment and through 3 months after the last dose of study treatment.
- Currently receiving treatment in another invasive investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
- Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
- Known CNS disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ascorbate.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known HIV-positive and hepatitis B \& C individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.
- Patients who are on warfarin and cannot have a drug substitution or who decline the drug substitution.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
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
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.
Read the 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
- Being tested
- Ascorbate
- Keywords
- Sarcoma, Soft tissue
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AscorbateDrug
Also called Ascorbic Acid, Vitamin C, Pharmacological 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
| Study group | Role | What they receive |
|---|---|---|
| Phase I dose escalation cohort | Experimental | Participants 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. Receives: Drug: Ascorbate |
| Phase II Cohort | Experimental | Participants 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. Receives: Drug: Ascorbate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Experienced Dose Limiting Toxicities (DLTs) Using CTCAE, Version 4.0
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.
Measured: Start of treatment up to 4 weeks after the last ascorbate infusion
Number of Participants With Pathologic Tumor Necrosis ≥ 95% Following Concurrent Radiation Therapy and Ascorbate
To estimate the efficacy of neoadjuvant ascorbate and radiotherapy as assessed by the pathological complete response rates (pCR) in subjects with locally advanced high grade soft tissue sarcomas.
Measured: Start of treatment up to 6 weeks after the last ascorbate infusion
Secondary outcomes (6)
Event-Free Survival at 2 Years
Event-free survival is defined as the time from treatment initiation until progression which precludes surgery, recurrence or death due to any cause. Otherwise, patients are censored at last disease assessment.
Measured: Enrollment or start of treatment up to 2 years following end of treatment
Overall Response Rate
Overall response rate (ORR) is the percentage of patients with a complete or partial response preoperatively as measured by RECIST 1.1 or a later tool for monitoring disease progression.
Measured: Enrollment or start of treatment up to 2 years following end of treatment
Overall Survival at 2 Years
Overall survival is defined as the time from treatment initiation to death due to any cause. Patients still alive are censored at last date known to be alive.
Measured: Enrollment or start of treatment up to 2 years following end of treatment
Skin Toxicity
Pathologist to grade radiation related skin toxicity.
Measured: Within two years following end of treatment
Labile Iron
To measure labile iron using T2* imaging sequence on MRI pre and post ascorbate treatments and compare with serum iron measurements
Measured: Within two years following end of treatment
Evaluate Diffusion Weighted Imaging Sequences
To evaluate diffusion weighted imaging sequences on MRI in pre and post treatment tumors and correlate it with necrosis and survival
Measured: Within two years following end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2018
- Study start27 Jun 2019
- Primary completion3 Jun 2022
- Study completion2 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mohammed Milhem
- Sponsor type
- University, hospital or other
- Collaborators
- University of Iowa
- Responsible party
- Sponsor-investigator, Mohammed Milhem, University of Iowa
- Investigators
- Mohammed Milhem, MBBS, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03508726
- Sponsor's protocol ID
- 201901810
- Status last verified
- May 2026
- First submitted
- 13 Apr 2018
- Last updated
- 18 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No