Soft Tissue Sarcoma
Conditions
Keywords
Grade II sarcoma, Grade III sarcoma
Brief summary
The purpose of this Phase 1 research study is to obtain data or information on the safety and effectiveness of the combination of gemcitabine, docetaxel with radiation.
Detailed description
Primary Objective: • To determine the maximum tolerated doses Gemcitabine and Taxotere when given weekly with concurrent radiation in the neoadjuvant setting for patients with soft tissue sarcoma of the extremities. Secondary Objective: • To evaluate immunological changes induced by gemcitabine and docetaxel with radiation in patient with high risk-soft tissue sarcomas in blood. This would include T cell subsets, NK, and dendritic cells and tumor macrophages all of which make up the tumor microenvironment. Long term follow-up will occur every 3-4 months for 24 months in person or video consultation.
Interventions
DRUGGemcitabine
Gemcitabine will be administered on day 1 of each one-week cycle for 6 cycles concurrently with radiation to the extremity on a 3+3 escalating dose (100 mg/m² to 300 mg/m²)
DRUGDocetaxel
Docetaxel will be administered on day 1 of each one-week cycle for 6 cycles concurrently with radiation to the extremity (10 mg/m² to 25 mg/m²).
RADIATIONRadiation
Radiation is to be done with standard preop dose of 50 Gy but at lower doses per fraction. Thus 50.4 Gy in 28 FX. Radiation will be given for 5 days (Monday - Friday) every week for approx. 6 weeks.
PROCEDURESurgical Resection
Upon completing neoadjuvant chemotherapy plus radiation therapy, surgical resection will occur.
OTHERBlood draws
Before treatment, blood (about 2 tubes of 10 mls each) to better understand some aspects of participants' immune system before chemotherapy.
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a histologically or cytologically confirmed Grade II or III soft tissue sarcoma that is considered to be resectable and are candidates for pre-op radiation. * Age greater than or equal to 18 years. No children will be enrolled on this protocol. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or double-barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Patients taking concurrent hormonal therapy, biologic or other chemotherapy are excluded except women on hormonal contraceptives. * Patients taking an investigational agent are excluded. * Pregnant and nursing women are excluded. * Patients who require amputation for local control. * Patients who underwent unplanned excision or other previous surgery involving the affected extremity. * Patients with sarcoma subtypes for which established chemotherapeutic regimens exist. * History of radiation to the limb.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose Chemotherapy and Radiation | Up to 8 weeks | Maximum tolerated dose of Gemcitabine and Taxotere and radiation will be completed by monitoring toxicities and using the 3+3 dose escalation plan. |
| Number of Toxicity Incidences | 8 weeks post-surgery | Complication/side effects from the chemotherapy combination of gemcitabine and taxotere concurrent with radiation will be assessed by toxicity counts/rates presented descriptively by toxicity, severity, and dose level using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Immunological Changes in Blood | 8 weeks post-surgery | The effects of the treatment on the immune system will be analyzed using paired t-test or the non-parametric counterpart. Correlations between immune cells and immune factor levels will be assessed using Spearman correlation coefficient. All tests will be two-sided with a significance level of 0.05, and no adjustment for multiple comparisons will be made due to the exploratory nature of these studies. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShailaja Raj, MRCP
Wake Forest University Health Sciences
Outcome results
None listed