Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance and Small Safety-margins (PREMISS)
Primary Purpose
Soft Tissue Sarcoma of the Limb, AJCC Stage II and III
Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
IMRT/IGRT, Tumor resection, Brachytherapy
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma of the Limb focused on measuring Soft tissue sarcoma, Intensity-Modulated Radiation Therapy (IMRT), Tomotherapy, Safety Margins, Image-guided Radiation Therapy, Brachytherapy, interstitial
Eligibility Criteria
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.
Sites / Locations
- Klinikum rechts der IsarRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1 Arm
Arm Description
Stratum A: R0, primary wound closure Stratum B: R0, secondary wound closure Stratum C: R1, tertiary wound closure
Outcomes
Primary Outcome Measures
Wound Complication Rate
Wound Complication Rate up to 3 months after tumor resection
Secondary Outcome Measures
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)
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
Limb Functionality
as measured by the Musculoskeletal Tumor Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS)
Quality of Life
as measured by QLQ C30
Translational
Full Information
NCT ID
NCT01552239
First Posted
July 26, 2011
Last Updated
October 15, 2018
Sponsor
Technical University of Munich
1. Study Identification
Unique Protocol Identification Number
NCT01552239
Brief Title
Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance and Small Safety-margins
Acronym
PREMISS
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
October 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technical University of Munich
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma of the Limb, AJCC Stage II and III
Keywords
Soft tissue sarcoma, Intensity-Modulated Radiation Therapy (IMRT), Tomotherapy, Safety Margins, Image-guided Radiation Therapy, Brachytherapy, interstitial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1 Arm
Arm Type
Experimental
Arm Description
Stratum A:
R0, primary wound closure
Stratum B:
R0, secondary wound closure
Stratum C:
R1, tertiary wound closure
Intervention Type
Radiation
Intervention Name(s)
IMRT/IGRT, Tumor resection, Brachytherapy
Intervention Description
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
Primary Outcome Measure Information:
Title
Wound Complication Rate
Description
Wound Complication Rate up to 3 months after tumor resection
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Efficacy
Description
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)
Time Frame
2 years
Title
Safety
Description
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
Time Frame
2 years
Title
Limb Functionality
Description
as measured by the Musculoskeletal Tumor Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS)
Time Frame
2 years
Title
Quality of Life
Description
as measured by QLQ C30
Time Frame
2 years
Title
Translational
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Röper, MD
Phone
+49-89-4140
Ext
4509
Email
barbara.roeper@lrz.tu-muenchen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Röper, MD
Organizational Affiliation
Klinik für Strahlentherapie und Radiologische Onkologie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum rechts der Isar
City
Munich
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Röper, MD
Phone
49-89-4140
Ext
4502
Email
barbara.roeper@lrz.tu-muenchen.de
First Name & Middle Initial & Last Name & Degree
Michael Molls, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
26573139
Citation
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.
Results Reference
derived
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Preoperative Radiotherapy for Sarcomas of the Extremities With Intensity-Modulation, Image-Guidance and Small Safety-margins
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