A Phase II Trial of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults
Overview
- Phase
- Phase 2
- Intervention
- Ascorbate
- Conditions
- Sarcoma
- Sponsor
- Mohammed Milhem, MBBS
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Tumor Response
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Detailed Description
This study will enroll male and female patients 18 years old or older who have a 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 and neo-adjuvant therapy for the treatment of sarcoma, must have been given. 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. During screening, subjects will receive a test dose (15g) of ascorbate. If the test dose results in any toxicity \>/= CTCAE grade 3 or a significant medical event in the opinion of the principal investigator, the patient will be considered a screen failure. Subjects who pass screening will then receive ascorbate, 75g, 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 at least 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.
Investigators
Varun Monga, MD
Assistant Clinical Professor
University of Iowa
Eligibility Criteria
Inclusion Criteria
- •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
- •Patients must meet the following laboratory criteria:
- •Hematology:
- •Neutrophil count of \>1500/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
Exclusion Criteria
- •G6PD (glucose-6-phosphate dehydrogenase) deficiency
- •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 fingerstick 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. Use of effective means of contraception (men and women) in subjects of child-bearing potential
- •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.
Arms & Interventions
Gemcitabine + High-Dose Ascorbate
Subjects will receive ascorbate, 75g, 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.
Intervention: Ascorbate
Gemcitabine + High-Dose Ascorbate
Subjects will receive ascorbate, 75g, 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.
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Tumor Response
Time Frame: Every 2 months for first 6 months, then every 3 months up to 2 years post treatment
From first day of treatment to documented disease progression as described by RECIST 1.1 criteria. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
Secondary Outcomes
- Progression Free Survival(Every 2 months for first 6 months, then every 3 months up to 2 years post treatment)
- Overall Survival(Every 2 months for first 6 months, then every 3 months up to 2 years post treatment)
- Incidence of Adverse Events (AE) Per CTCAE 4.03(Up to 30 days after completion of study treatment)