Gemcitabine With Ascorbate Including Adolescents

NCT04877587 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 202009351
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Soft Tissue Sarcoma; Bone Sarcoma; Unresectable Soft Tissue Sarcoma; Metastatic Bone Sarcoma; Metastatic Soft-tissue Sarcoma; Unresectable Bone Sarcoma

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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

  For two years following completion of treatment

Secondary Outcomes (2)

• PFS defined by RECIST 1.1 guidelines

  For two years following completion of treatment

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

  For two years following completion of treatment

Study Arms (1)

Ascorbate in combination with Gemcitabine

EXPERIMENTAL

The 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.

Drug: Ascorbate; Drug: Gemcitabine

Interventions

Ascorbate DRUG

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)

Also known as: Vitamin C

Ascorbate in combination with Gemcitabine

Gemcitabine DRUG

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

Also known as: Gemzar®

Ascorbate in combination with Gemcitabine

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• David Dickens: lead

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

Ascorbic Acid; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• David Dickens, MD, FAAP

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 7, 2021
• Study Start: January 1, 2023
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: February 22, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)