Sarcoma Clinical Trial
Official title:
A Phase II Trial of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults
Verified date | November 2020 |
Source | University of Iowa |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 10 |
Est. completion date | October 19, 2020 |
Est. primary completion date | April 16, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Male or female patients aged = 18 years old 2. ECOG Performance Status of = 2 3. 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 - 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 - Total serum calcium >/= LLN or if calcium is below LLN then corrected calcium for serum albumin should be >/= LLN - Serum potassium = LLN - Serum sodium = LLN - Serum albumin = LLN or 3g/dl 4. Tolerate a 15g ascorbate infusion (screening dose) 5. Baseline MUGA or ECHO done only in subjects with prior doxorubicin exposure. The test must demonstrate LVEF = the lower limit of the institutional normal. 6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing 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 7. 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 and 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. 8. 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. 9. 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. 10. 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. Exclusion Criteria: 1. G6PD (glucose-6-phosphate dehydrogenase) deficiency 2. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) 3. History of myocardial infarction or unstable angina within 6 months prior to Day 1 4. History of stroke or transient ischemic attack within 6 months prior to Day 1 5. 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 6. 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). 7. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 8. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) 9. Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential 10. 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. 11. Other concurrent severe and/or uncontrolled medical conditions 12. 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. 13. 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. 14. Concomitant use of any anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted. 15. Male patients whose sexual partners are WOCBP 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. 16. 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 17. 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. 18. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent. 19. Patients with GIST tumors and Kaposi's Sarcoma are excluded. 20. 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. |
Country | Name | City | State |
---|---|---|---|
United States | University of Iowa Hospitals and Clinics | Iowa City | Iowa |
Lead Sponsor | Collaborator |
---|---|
Mohammed Milhem, MBBS | St. Baldrick's Foundation, University of Iowa, University of Iowa Adolescent and Young Adult (AYA) Cancer Program |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Tumor Response | 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. | Every 2 months for first 6 months, then every 3 months up to 2 years post treatment | |
Secondary | Progression Free Survival | Time from start of therapy (day 1, cycle 1) to documented disease progression or death due to any cause. Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST. | Every 2 months for first 6 months, then every 3 months up to 2 years post treatment | |
Secondary | Overall Survival | Time from start of therapy (day 1, cycle 1) to death. | Every 2 months for first 6 months, then every 3 months up to 2 years post treatment | |
Secondary | Incidence of Adverse Events (AE) Per CTCAE 4.03 | Categorize and quantify adverse events from start of therapy (day 1, cycle 1) to end of study per (CTCAE) version 4.03. | Up to 30 days after completion of study treatment |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04986748 -
Using QPOP to Predict Treatment for Sarcomas and Melanomas
|
||
Recruiting |
NCT04457258 -
68Ga-FAPi-46 PET/CT Scan in Imaging Patients With Sarcoma
|
Early Phase 1 | |
Completed |
NCT04474678 -
Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!")
|
N/A | |
Recruiting |
NCT05415098 -
Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Recruiting |
NCT04535713 -
GALLANT: Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma
|
Phase 2 | |
Completed |
NCT03521531 -
Burden and Medical Care of Sarcoma in Germany
|
||
Completed |
NCT02496520 -
Dendritic Cell-based Immunotherapy for Advanced Solid Tumours of Children and Young Adults
|
Phase 1/Phase 2 | |
Terminated |
NCT02054104 -
Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum
|
Phase 1/Phase 2 | |
Terminated |
NCT00788125 -
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Active, not recruiting |
NCT04577014 -
Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma
|
Phase 1/Phase 2 | |
Completed |
NCT04052334 -
Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma
|
Phase 1 | |
Completed |
NCT01593748 -
A Phase II Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma
|
Phase 2 | |
Completed |
NCT00199849 -
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine
|
Phase 1 | |
Recruiting |
NCT04367779 -
Research of Biomarkers of Response to Proton Beam Therapy in Pediatric and Adult Patients.
|
||
Completed |
NCT01879085 -
Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
|
Phase 1/Phase 2 | |
Recruiting |
NCT04553692 -
Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers
|
Phase 1 | |
Completed |
NCT01209598 -
PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
|
Phase 2 | |
Completed |
NCT04553471 -
Palliative Lattice Stereotactic Body Radiotherapy (SBRT) for Patients With Sarcoma, Thoracic, Abdominal, and Pelvic Cancers
|
N/A | |
Withdrawn |
NCT04906876 -
A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
|
Phase 2 |