Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance and Small Safety-margins (PREMISS)

Phase II Study of Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance, Small Safety-margins and Brachytherapy Conditioned by Resection Margin

RATIONALE: Modern radiotherapy techniques in a neoadjuvant setting have the potential to minimize morbidity and maximize efficacy. An additional boost dose can be provided locally by HDR-brachytherapy in patients with positive margins after tumor resection.

PURPOSE: This phase II trial is studying the safety and efficacy of a combination of modern radiotherapy elements applied to the tumor and small volumes of surrounding normal tissue (IMRT, IGRT; brachytherapy in case of positive resection margin) and see how well it works in treating patients with High-Risk Soft Tissue Sarcoma of the Extremities.

Study Overview

• Status: Unknown
• Conditions: Soft Tissue Sarcoma of the Limb; AJCC Stage II and III
• Intervention / Treatment: Radiation: IMRT/IGRT, Tumor resection, Brachytherapy

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar
    • Contact: Barbara Röper, MD; Phone Number: 4502 49-89-4140; Email: barbara.roeper@lrz.tu-muenchen.de
    • Sub-Investigator: Michael Molls, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Histologic and radiographic proof of localized high-risk soft tissue sarcoma meeting the following criteria:

• Lesion originates in extremity

  • upper extremity lesions may occur from the medial border of the scapula to tumors as far distal as the finger tips
  • lower extremity regions include hip girdle tumors commencing at the iliac crest, excluding lesions arising from within the pelvis, and extends to include lesions as far distal as the toes
• AJCC Stage II or III disease (except T1a-tumors or N1)
• Primary presentation or local recurrence
• after biopsy or inadequate surgery resulting in residual tumor in cross-sectional imaging
• Tumors must be considered resectable according to cross sectional imaging, or potentially resectable after preoperative radiotherapy
• ECOG Performance Status 0-2
• Informed Consent

Exclusion Criteria:

• Diagnosis of the following:

  • Primitive neuroectodermal tumor
  • Soft tissue Ewing's sarcoma
  • Extraskeletal osteo- or chondrosarcoma
  • Aggressive fibromatosis (desmoid tumors)
  • Dermatofibrosarcoma protuberans
• Regional nodal disease or unequivocal distant metastasis
• Life expectancy < 1 year
• Pregnancy
• Major medical illness that would preclude study treatment
• History of major wound complication or recurrent skin infection
• Known HIV positivity
• < 2 weeks elapsed from prior surgery or cytotoxic chemotherapy
• persisting acute toxicities > grade 1 in tumor-bearing limb resulting from prior treatment with anti-cancer modalities
• Cytotoxic chemotherapy, targeted therapy or investigational agents concurrent to study treatment
• Prior radiotherapy to the site of present STS.
• Chronic requirement for treatment with immuno¬suppressive agents or steroids.

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: 1 Arm; Stratum A: R0, primary wound closure Stratum B: R0, secondary wound closure Stratum C: R1, tertiary wound closure

Radiation: IMRT/IGRT, Tumor resection, Brachytherapy; All: Preoperative IMRT with small safety margins (GTV according to MRT plus 1.5cm laterally / 3cm proximodistally) to 50Gy total dose, 2 Gy single dose, 5 fractions per week, daily IGRT with in-room CT (Tomotherapy) Tumor resection after 4-6 weeks Stratum C: Interstitial Brachytherapy to tumor bed with 15 Gy total dose, 3 Gy single dose b.i.d. in second week after tumor resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Complication Rate	Wound Complication Rate up to 3 months after tumor resection	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Efficacy: Rate of margin-free resection Local control rate (LC) Metastasis-Free Survival (MFS) Disease-Free Survival (DFS) Disease-Specific Survival, Overall Survival (OS) Limb Preservation Rate (LP)	2 years
Safety	Acute toxicity as measured by CTCAE v. 4.03 Late toxicity (skin, soft tissue, joint, bone, neural toxicity) as measured by CTCAE v. 4.03	2 years
Limb Functionality	as measured by the Musculoskeletal Tumor Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS)	2 years
Quality of Life	as measured by QLQ C30	2 years
Translational		2 years

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Barbara Röper, MD, Klinik für Strahlentherapie und Radiologische Onkologie

Publications and helpful links

General Publications

• Roper B, Heinrich C, Kehl V, Rechl H, Specht K, Wortler K, Topfer A, Molls M, Kampfer S, von Eisenharth-Rothe R, Combs SE. Study of Preoperative Radiotherapy for Sarcomas of the Extremities with Intensity-Modulation, Image-Guidance and Small Safety-margins (PREMISS). BMC Cancer. 2015 Nov 16;15:904. doi: 10.1186/s12885-015-1633-y.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): October 1, 2019

Study Registration Dates

• First Submitted: July 26, 2011
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Brachytherapy; interstitial; Soft tissue sarcoma; Intensity-Modulated Radiation Therapy (IMRT); Tomotherapy; Safety Margins; Image-guided Radiation Therapy
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: PRE-1205-ROE-0050-I; No. 2009.906.1 (Other Grant/Funding Number: Wilhelm-Sander-Stiftung)

Drug and device information, study documents

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