SarcomaEarly Phase 1NCT04634227
Gemcitabine Plus Ascorbate for Sarcoma in Adults (Pilot)
A Early Phase 1 study testing Ascorbate in people with Sarcoma and Soft Tissue Sarcoma, run by University of Iowa at 1 site in United States.
Trial summary
This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma, Soft Tissue Sarcoma, Unresectable 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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Nov 2020to 31 Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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
- Male or female patients aged ≥ 18 years old
- ECOG Performance Status of ≤ 2
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Tolerate a 15g ascorbate infusion (screening dose)
- Any patient with the diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except GIST and Kaposi's) from any site. A minimum of 1 prior chemotherapy regimen, including adjuvant or neo-adjuvant therapy for the treatment of sarcoma. Patients eligible for an anthracycline should have received a prior anthracycline containing regimen. Patients who decline or are not eligible for anthracycline treatment may be considered for this protocol as a first line treatment. Patients with a diagnosis of liposarcoma should also have received eribulin if they received anthracycline-based therapy prior to eribulin. Patients with a diagnosis of myxoid liposarcoma should have received trabectedin. Patients with angiosarcoma should have received either taxol or docetaxel. Patients must have measurable disease defined as at least 1 lesion ≥ 1cm in the greatest dimension.
- Patients with metastatic bone sarcomas who have failed all available therapies that have demonstrated clinical benefit. Available therapies include but not limited to methotrexate, adriamycin and cisplatin for osteosarcoma and vincristine, adriamycin and Cytoxan, ifosfamide, etoposide (VAC/IE) for Ewing's sarcoma.
- Patients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with locally advanced unresectable or metastatic disease.
- Patients with NO 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
Who cannot join
- Lab values in the below ranges:
- Neutrophil count of </=1500/mm3
- Platelet count of </= 100,000/mm3L
- Hemoglobin < 9 g/dL (transfusion to meet eligibility allowed)
- AST/SGOT and ALT/SGPT > 2.5 x upper limit of normal (ULN) or >5.0 x ULN if the transaminase elevation is due to disease involvement
- Alkaline phosphatase > 5 x ULN without known bony metastases
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- Serum bilirubin >1.5 x ULN
- Serum creatinine > 1.5 x ULN or 24-hour creatinine clearance <50 ml/min
- Total serum calcium < LLN or if calcium is below LLN then corrected calcium for serum albumin should be >/= LLN
- Serum potassium < 3.0
- Serum sodium < 130
- Serum albumin <2.5g/dl
- G6PD (glucose-6-phosphate dehydrogenase) deficiency
- Prior exposure to gemcitabine for metastatic disease
- Subjects with prior doxorubicin exposure with a MUGA or ECHO demonstrating LVEF < the lower limit of the institutional normal.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Actively receiving insulin or requiring fingerstick glucose monitoring at time of ascorbate infusion
- Patients on warfarin and unable to be substituted to another anticoagulant
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Pregnancy (positive pregnancy test) or lactation.
- Women of childbearing potential (WOCBP) who are not willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration
- 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.
- Other concurrent severe and/or uncontrolled medical conditions
- Patients who have received chemotherapy or any investigational drug < 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study.
- Concomitant use of any other anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted.
- Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
- Patients with a history of another primary malignancy within 2 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
- Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.37
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Patients with history of more than one symptomatic oxalate stone in the last 6 months or visible stone in the kidney or ureter on screening CT scan.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults
This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site.
Read the detailed description
The primary objectives of this pilot study are to assess the feasibility of pharmacokinetically-guided, patient-individualized dosing and to obtain preliminary evidence of anti-tumor activity of intravenous ascorbate in combination with gemcitabine to inform a subsequent Phase II trial. Soft tissue and bone sarcomas will be studied as different cohorts given the differences in biology and historical responses to single agent gemcitabine in these disease types. As such, 10 evaluable patients per disease cohort will be included.
- Conditions
- Sarcoma, Soft Tissue Sarcoma, Unresectable Soft Tissue Sarcoma, Metastatic Bone Tumor, Bone Sarcoma
- Being tested
- Ascorbate
- Keywords
- Sarcoma, Soft tissue, Ascorbate
- Medical subject headings
- Sarcoma, Bone Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AscorbateDrug
Following 15g test dose, 75g administered 75g dose on days 1 and 2. Further doses of ascorbate will be determined by serum ascorbate levels measured by the end of the week to reach a target serum concentration between 20 -30 mM. Ascorbate doses will continue to be escalated until either the target serum concentration or maximum dose of 125 g is administered.
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine + High-Dose Ascorbate | Experimental | Ascorabte is administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator. Treatment will be terminated with progression of disease. Disease will be assessed by CT of the chest, abdomen and pelvis or MRI of the lesion every 2 cycles for progression. Receives: Drug: Ascorbate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the 12 weeks progression free survival (PFS 12) at 12 weeks post treatment initiation
The primary endpoint of interest is PFS12 defined as the proportion of patients without progressive disease per RECIST 1.1 at 12 weeks after treatment initiation. A sample size of 10 evaluable patients per disease cohort (soft tissue and bone) will allow for the estimation of PFS12 per the 90% exact confidence intervals as follows:
PFS12 Exact 90% confidence interval:
1/10 10% (1-39%); 2/10 20% (4-51%); 3/10 30% (9-61%); 4/10 40% (15-70%); 5/10 50% (22-78%); 6/10 60% (30-85%); 7/10 70% (39-91%); 8/10 80% (49-96%); 9/10 90% (61-99%);
Measured: 12 weeks post-treatment
Secondary outcomes (3)
Assess overall survival of patients with unresectable or metastatic soft tissue and bone sarcoma treated with high dose ascorbate when administered intravenously concurrently with gemcitabine
Time from start of therapy (day 1, cycle 1) to death.
Measured: Every 2 months for first 6 months, then every 3 months up to 2 years post treatment
Determine the tumor response as per RECIST 1.1 criteria
Tumor response will be defined using the RECIST 1.1 guidelines as below
- Complete response is the disappearance of all target lesions; Any pathological lymph nodes ( whether target or Non-target) must have reduction in short axis to <10mm.
- Partial response is a 30% decrease in the sum of the longest dimension (LD) of target lesions, relative to baseline measurement;
- Progressive disease is an increase of 20% or more in the sum of the LD of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm.Or appearance of a new malignant lesion.
- Stable disease is a decrease in tumor size of less than 30% or increase of less than 20%.
Measured: 12 weeks post-treatment
Incidence of Adverse Events (AE) Per CTCAE 4.03
Evaluate the safety and tolerability of this regimen by the incidence of AEs per CTCAE 4.03
Measured: Up to 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start24 Nov 2020
- Primary completion18 Mar 2025
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- Mohammed Milhem, MBBS
- Responsible party
- Principal investigator, John Rieth, University of Iowa
- Investigators
- John Rieth, MD, Principal investigator, University of Iowa Hospitals & Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04634227
- Sponsor's protocol ID
- 201802800 (Pilot)
- Status last verified
- May 2026
- First submitted
- 16 Nov 2020
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults
- ClinicalTrials.gov ID
- NCT04634227
- Acronym / sponsor ID
- 201802800 (Pilot)
- Conditions
- Sarcoma, Soft Tissue Sarcoma, Unresectable Soft Tissue Sarcoma, Metastatic Bone Tumor, Bone Sarcoma
- Keywords
- Sarcoma, Soft tissue, Ascorbate
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- Mohammed Milhem, MBBS
- Study start
- 24 Nov 2020 (actual)
- Primary completion
- 18 Mar 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site.
Detailed description
The primary objectives of this pilot study are to assess the feasibility of pharmacokinetically-guided, patient-individualized dosing and to obtain preliminary evidence of anti-tumor activity of intravenous ascorbate in combination with gemcitabine to inform a subsequent Phase II trial. Soft tissue and bone sarcomas will be studied as different cohorts given the differences in biology and historical responses to single agent gemcitabine in these disease types. As such, 10 evaluable patients per disease cohort will be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine + High-Dose Ascorbate | Experimental | Drug: AscorbateAscorabte is administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator. Treatment will be terminated with progression of disease. Disease will be assessed by CT of the chest, abdomen and pelvis or MRI of the lesion every 2 cycles for progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients aged ≥ 18 years old
- ECOG Performance Status of ≤ 2
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Tolerate a 15g ascorbate infusion (screening dose)
- Any patient with the diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except GIST and Kaposi's) from any site. A minimum of 1 prior chemotherapy regimen, including adjuvant or neo-adjuvant therapy for the treatment of sarcoma. Patients eligible for an anthracycline should have received a prior anthracycline containing regimen. Patients who decline or are not eligible for anthracycline treatment may be considered for this protocol as a first line treatment. Patients with a diagnosis of liposarcoma should also have received eribulin if they received anthracycline-based therapy prior to eribulin. Patients with a diagnosis of myxoid liposarcoma should have received trabectedin. Patients with angiosarcoma should have received either taxol or docetaxel. Patients must have measurable disease defined as at least 1 lesion ≥ 1cm in the greatest dimension.
Key exclusion criteria (34 listed)
- Lab values in the below ranges:
- G6PD (glucose-6-phosphate dehydrogenase) deficiency
- Prior exposure to gemcitabine for metastatic disease
- Subjects with prior doxorubicin exposure with a MUGA or ECHO demonstrating LVEF < the lower limit of the institutional normal.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AscorbateFollowing 15g test dose, 75g administered 75g dose on days 1 and 2. Further doses of ascorbate will be determined by serum ascorbate levels measured by the end of the week to reach a target serum concentration between 20 -30 mM. Ascorbate doses will continue to be escalated until either the target serum concentration or maximum dose of 125 g is administered. | Drug | Gemcitabine + High-Dose Ascorbate |
Primary outcome
Determine the 12 weeks progression free survival (PFS 12) at 12 weeks post treatment initiation
Time frame: 12 weeks post-treatment
The primary endpoint of interest is PFS12 defined as the proportion of patients without progressive disease per RECIST 1.1 at 12 weeks after treatment initiation. A sample size of 10 evaluable patients per disease cohort (soft tissue and bone) will allow for the estimation of PFS12 per the 90% exact confidence intervals as follows: PFS12 Exact 90% confidence interval: 1/10 10% (1-39%); 2/10 20% (4-51%); 3/10 30% (9-61%); 4/10 40% (15-70%); 5/10 50% (22-78%); 6/10 60% (30-85%); 7/10 70% (39-91%); 8/10 80% (49-96%); 9/10 90% (61-99%);
3 secondary outcomes
Assess overall survival of patients with unresectable or metastatic soft tissue and bone sarcoma treated with high dose ascorbate when administered intravenously concurrently with gemcitabine
Time frame: Every 2 months for first 6 months, then every 3 months up to 2 years post treatment
Determine the tumor response as per RECIST 1.1 criteria
Time frame: 12 weeks post-treatment
Incidence of Adverse Events (AE) Per CTCAE 4.03
Time frame: Up to 30 days after completion of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Rieth, MD principal investigator
University of Iowa Hospitals & Clinics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ascorbate in people with Sarcoma and Soft Tissue Sarcoma, run by University of Iowa at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the 12 weeks progression free survival (PFS 12) at 12 weeks post treatment initiation (time frame: 12 weeks post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.