Gemcitabine and Docetaxel With Radiation in Adults With Soft Tissue Sarcoma of the Extremities

Phase I Trial Study of Gemcitabine and Docetaxel With Radiation in Adult Patients With High Grade and Greater Than 5 cm Soft Tissue Sarcoma of the Extremities

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.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Docetaxel; Radiation: Radiation; Procedure: Surgical Resection; Other: Blood draws

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.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ashley Fansler, RN; Phone Number: 336-716-5440; Email: arcarrol@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Contact: Ashley Fansler, RN
      • Principal Investigator: Shailaja Raj, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Chemotherapy Plus Radiation Therapy; Up to 6 cycles (once a week) of chemotherapy with a 3+3 dose escalating plan (from 100 mg to 300 mg for Gemcitabine; 10 mg to 25 mg for Docetaxel) along with radiation (five days a week) for up to 6 weeks.

Drug: Gemcitabine; 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); Drug: Docetaxel; 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).; Other Names: Taxotere; Radiation: Radiation; 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.; Procedure: Surgical Resection; Upon completing neoadjuvant chemotherapy plus radiation therapy, surgical resection will occur.; Other: Blood draws; Before treatment, blood (about 2 tubes of 10 mls each) to better understand some aspects of participants' immune system before chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose Chemotherapy and Radiation	Maximum tolerated dose of Gemcitabine and Taxotere and radiation will be completed by monitoring toxicities and using the 3+3 dose escalation plan.	Up to 8 weeks
Number of Toxicity Incidences	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.	8 weeks post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Immunological Changes in Blood	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.	4 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Shailaja Raj, MRCP, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Grade II sarcoma; Grade III sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Gemcitabine
• Other Study ID Numbers: IRB00061621; P30CA012197 (U.S. NIH Grant/Contract); CCCWFU 71117 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No