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Soft Tissue SarcomaEarly Phase 1NCT04877587

Gemcitabine With Ascorbate Including Adolescents

A Early Phase 1 study testing Ascorbate and Gemcitabine in people with Soft Tissue Sarcoma and Bone Sarcoma, run by David Dickens at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this research study is to see if a high dose of ascorbate (Vitamin C), in combination with the chemotherapy drug gemcitabine, is safe and effective in adolescents with locally advanced unresectable or metastatic soft tissue and bone sarcomas Read more about this study

Who is it for?
Ages 13 to 17 years
What is being tested?
Ascorbate and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jan 2023to 31 May 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

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 13 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Male or female patients aged ≥ 13 years to 17 years
  • ECOG Performance Status of ≤ 2
  • Ability to provide written informed consent from patient guardian and informed assent from patient; obtained prior to participation in the study and any related procedures being performed
  • Tolerate a 10g 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.
  • Previous exposure to Gemcitabine will only be allowed if there is no residual toxicity from previous treatments. Toxicity must be graded as 0 or 1 prior to study.
  • 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.

Who cannot join

  • Inadequate organ function as defined by:
  • Hematology:
  • Neutrophil count of </=1,000/mm3
  • Platelet count of </= 100,000/mm3L
  • Hemoglobin < 9 g/dL (transfusion to meet eligibility allowed)
  • Biochemistry:
Show all 32Show fewer
  • 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
  • Serum bilirubin > 1.5 x ULN
  • Serum creatinine > 1.5 x ULN or 24-hour creatinine clearance < 50 ml/min
  • G6PD (glucose-6-phosphate dehydrogenase) deficiency
  • Baseline MUGA or ECHO < than the lower limit of the institutional normal. ECHO or MUGA only done on patients with prior doxorubicin exposure.
  • 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
  • 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
  • Actively receiving insulin or requiring finger stick glucose monitoring at time of ascorbate infusion (unless an exception is granted by the IND sponsor, medical monitor, and the PI).
  • 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.
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, warfarin 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 anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted.
  • Females of childbearing potential (FOCBP) who are unwilling 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
  • Male patients whose sexual partners are FOCBP 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 GIST tumors and Kaposi sarcoma are excluded
  • 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.

United States1 site

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

Other trials in United States

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 Including Adolescents

The purpose of this research study is to see if a high dose of ascorbate (Vitamin C), in combination with the chemotherapy drug gemcitabine, is safe and effective in adolescents with locally advanced unresectable or metastatic soft tissue and bone sarcomas

Read the detailed description

The primary objective of the expansion cohort of this pilot study is to evaluate preliminary evidence of anti-tumor activity of intravenous ascorbate in combination with gemcitabine as assessed by overall response rate to inform a subsequent Phase II trial.

Being tested
Ascorbate, Gemcitabine
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

    Also called Vitamin C

    A patient-individualized pharmacokinetically-guided dose escalation design will be used for Ascorbate. The goal of the within-patient dose escalation is to achieve a target plasma ascorbate level between 20mM and 30mM. The administered dose levels under consideration are listed below.

    Dose Level Ascorbate

    • 2 60 g/m2 IV Days (1,2,8,9,15,16)
    • 1 50 g/m2 IV Days (1,2,8,9,15,16) 0 (Starting dose) 40 g/m2 IV Days (1,2,8,9,15,16)
    • 1 30 g/m2 IV Days (1,2,8,9,15,16)

  • GemcitabineDrug

    Also called Gemzar®

    Gemcitabine 900 mg/m2 given at a fixed dose rate of 10 mg/m2/min on D1, D8 and D15 to be given over 90 min every 28 days

Study groups in NCT04877587
Study groupRoleWhat they receive
Ascorbate in combination with GemcitabineExperimentalThe study will begin with a safety run-in. A patient-individualized pharmacokinetically-guided dose escalation design will be used for Ascorbate. Gemcitabine is administered following standard fixed dose infusion practice adopted at The University of Iowa Hospitals \& Clinics. Ascorbate is infused prior to gemcitabine. Cycles are 28 days. Patients will be treated for a total of 6 cycles and assessed every 2 cycles for disease response.
Receives: Drug: Ascorbate; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Events as defined by CTCAE version 5.0

    Occurrence of adverse events as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of all adverse events will be summarized by simple descriptive statistics.

    Measured: Adverse events will be followed for 4 weeks after the last pharmacologic ascorbate infusion

  2. ORR as defined by RECIST 1.1 guidelines

    Overall Response Rate (ORR) as defined by the percentage of patients with a complete or partial response, according to RECIST 1.1 guidelines

    Measured: For two years following completion of treatment

Secondary outcomes (2)

  1. PFS defined by RECIST 1.1 guidelines

    Progression Free Survival (PFS) defined as the time from first day of study treatment to the first documented disease progression or death due to any cause, RECIST 1.1 guidelines

    Measured: For two years following completion of treatment

  2. OS defined as the time from first day of study treatment to death due to any cause

    Overall Survival (OS) defined as the time from first day of study treatment to death due to any cause

    Measured: For two years following completion of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2021
  2. Study startJan 2023 (estimated)
  3. Primary completion31 May 2025 (estimated)
  4. Study completion31 May 2025 (estimated)

Why it stopped: Unable to enroll

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04877587
Sponsor's protocol ID
202009351
Status last verified
Feb 2023
First submitted
30 Apr 2021
Last updated
22 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Ascorbate and Gemcitabine in people with Soft Tissue Sarcoma and Bone Sarcoma, run by David Dickens 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 32 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: withdrawn, as of the sponsor's last update on 22 Feb 2023. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Adverse Events as defined by CTCAE version 5.0 (time frame: Adverse events will be followed for 4 weeks after the last pharmacologic ascorbate infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04877587.

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 Feb 2023.

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