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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
John
Iowa City, Iowa, United States
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%);
Time frame: 12 weeks post-treatment
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.
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
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%.
Time frame: 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
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Time frame: Up to 30 days after completion of study treatment