Gemcitabine Plus Ascorbate for Sarcoma in Adults (Pilot)

NCT04634227 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 201802800 (Pilot)
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sarcoma; Soft Tissue Sarcoma; Unresectable Soft Tissue Sarcoma; Metastatic Bone Tumor; Bone Sarcoma

Keywords

Sarcoma; Soft tissue; Ascorbate

Outcome Measures

Primary Outcomes (1)

• 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%);

  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

  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

  12 weeks post-treatment

• Incidence of Adverse Events (AE) Per CTCAE 4.03

  Up to 30 days after completion of study treatment

Study Arms (1)

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.

Drug: Ascorbate

Interventions

Ascorbate DRUG

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.

Gemcitabine + High-Dose Ascorbate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Iowa: lead
• Mohammed Milhem, MBBS: collaborator

Study Sites (1)

John

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• John Rieth, MD

  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: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: November 18, 2020
• Study Start: November 24, 2020
• Primary Completion: March 18, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)