Skip to content
Triangle logo TriangleGet started
← Study library

NCT01710176 · CITED IN SOURCE DOCUMENTS

Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2025-11-18

This is a randomized Phase III clinical trial in the setting of localized high-risk soft tissue sarcomas (STS). This study will compare a standard neoadjuvant chemotherapy with epirubicin plus ifosfamide versus a histology-driven chemotherapy, i.e. a chemotherapy tailored to the specific histology within the family of adult STS. Chemotherapy will be administered for 3 cycles. There will be five histological groups (representing 80% of STS), as follows: leiomyosarcoma, myxoid liposarcoma with hypercellularity (round cell MLPS), synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST) and undifferentiated pleomorphic sarcoma. The histology-driven chemotherapy for these groups will be, respectively, gemcitabine plus dacarbazine, trabectedin, high-dose ifosfamide, ifosfamide plus etoposide, gemcitabine plus docetaxel. Other histological groups will also be included and registered, but treated only by standard chemotherapy. Patients who have already undergone definitive surgery will receive treatment post-operatively and patients needing a re-excision after inadequate surgery will be treated as patients in the two groups, but of course will not be evaluable for response. A centralized pathological review will be performed. Radiological response will be evaluated according to RECIST and to Choi criteria. Pathological response will also be recorded. The endpoint will be disease-free survival (DFS) and, secondarily, overall survival (OS) of patients receiving standard chemotherapy versus those receiving histotype-tailored chemotherapy. Additional aims will be to compare the probability of response of standard vs histotype-tailored chemotherapy and to determine the radiological and pathological response with standard chemotherapy vs tailored chemotherapy in each different histological group. Another aim will be to validate the response (both radiological and pathological) to preoperative chemotherapy as a surrogate endpoint for DFS and OS. Three hundred patients will be randomized over a 3-years period, from a pool of 400-450 registered patients. Translational research will be performed. Areas of research will include identification and validation of the potential predictive markers for each histological subgroups. The study is designed to verify the statistical hypothesis that histotype-tailored approach is associated, overall, with a 30% reduction in the hazard of relapse. However, in each different histological group, the effect of histotype-tailored chemotherapy, as compared to standard chemotherapy, can be different. To address this weakness an orthogonal study of response to chemotherapy as a surrogate of DFS and OS has been introduced into the trial. This study intends to extensively investigate the response (radiological and pathological) to preoperative chemotherapy and to validate it as a surrogate endpoint by showing that it correlates with disease free survival and overall survival.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: 1. Soft tissue sarcoma of adults, primary or locally recurrent, with spindle-cell or pleomorphic histology, belonging to one of the following for the randomization (Group1): myxoid-Round Cell liposarcoma (cellular component \>5 %), leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheat tumor, undifferentiated pleomorphic sarcoma (ex Malignant fibrous histiocytoma) Or belonging to one of the following for the registration (Group 2): myxofibrosarcoma, unclassified Spindle Cell, pleomorphic liposarcoma, pleomorphic rabdomiosarcoma Or belonging to either group but not being evaluable for response (re-excision after previous inadequate resection or primary definitive surgery) (Group3). The histological diagnosis must be made according to the WHO criteria and will have to be centrally reviewed before randomization. 2. High malignancy grade: grade 3 of 3, according to Coindre, or grade 2 at biopsy with a radiological evidence of more than 50% of necrosis in the tumor mass. 3. Deep seated extremities, girdles and/or superficial trunk (thoracic or abdominal wall)lesion. 4. Size of primary tumor (visible or previously inadequately resected) \>5 cm at instrumental staging (CT, MRI), or locally recurrent of any size. 5. Age \> 18 years. 6. ECOG performance status \<1. 7. Adequate bone marrow function: WBC \>3.500/mm3 neutrophil \>1.500/mm3 platelets \>150.000/mm3 hemoglobin \>11 g%. 8. Adequate renal (creatinine \<1.3 mg%), and hepatic function (bilirubin \<1.5 mg% and transaminases \<2 x n.v. If ALP \> 2.5 x ULN, ALP LF and/or GGT \< ULN). 9. Adequate cardiac function (FE \>50%). 10. Signed informed consent. 11. Complete compliance of the participating center with the protocol requirements. Exclusion Criteria: 1. Pregnancy or lactation. 2. Distant metastasis. 3. Other malignancies within past 5 years, with the exception of carcinoma in situ of cervix and basocellular skin cancers treated with eradicating intent. 4. Sarcoma histotypes other than those mentioned in the inclusion criteria. 5. Prior CT and/or RT. 6. Serious psychiatric disease that precludes informed consent or limits compliance. 7. Medical disease limiting survival to less than two years, limiting compliance or which in the physician's opinion might interfere significantly with the toxicity of the treatments. 8. Cardiovascular diseases resulting in a New York Heart Association Functional Status \> 2. 9. Uncontrolled bacterial, viral or fungal infection. 10. Impossibility of ensuring adequate follow-up. 11. Failure to comply with the requirements of the present protocol leading to exclusion of the participating center.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Standard arm foresees 3 cycles of preoperative chemotherapy, each cycle will be repeated every 21 days and includes: epirubicin 60 mg/m2/day, short infusion, days 1 and 2; ifosfamide 3 g/m2/day, days 1, 2, 3
    intervention Names
    1. Drug: epirubicin 60 mg/m2/day (days 1, 2) and ifosfamide 3 g/m2/day (days 1, 2, 3)
    label
    standard chemotherapy with full-dose epirubicin + ifosfamide
    type
    ACTIVE_COMPARATOR
  2. description
    gemcitabine+docetaxel for undifferentiated pleomorphic sarcoma, trabectedin for myxoid liposarcoma with hypercellularity, ifosfamide for synovial sarcoma, ifosfamide+etoposide for malignant peripheral nerve sheath tumor, gemcitabine+dacarbazine for leiomyosarcoma
    intervention Names
    1. Drug: gemcitabine 900 mg/m2 (days 1 and 8) and docetaxel 75 mg/m2 (day 8)
    2. Drug: trabectedin 1.3 mg/m2
    3. Drug: high-dose ifosfamide 14 g/m2, given in in 14 days
    4. Drug: etoposide 150 mg/m2/day (days 1, 2, 3) and ifosfamide 3g/m2/day (days 1, 2, 3)
    5. Drug: gemcitabine 1800 mg/m2 (day 1) and dacarbazine 500 mg/m2 (day 1)
    label
    histotype-tailored chemotherapy according to the histotype
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. standard chemotherapy with full-dose epirubicin + ifosfamide
    name
    epirubicin 60 mg/m2/day (days 1, 2) and ifosfamide 3 g/m2/day (days 1, 2, 3)
    type
    DRUG
  2. arm Group Labels
    1. histotype-tailored chemotherapy according to the histotype
    name
    gemcitabine 900 mg/m2 (days 1 and 8) and docetaxel 75 mg/m2 (day 8)
    type
    DRUG
  3. arm Group Labels
    1. histotype-tailored chemotherapy according to the histotype
    name
    trabectedin 1.3 mg/m2
    type
    DRUG
  4. arm Group Labels
    1. histotype-tailored chemotherapy according to the histotype
    name
    high-dose ifosfamide 14 g/m2, given in in 14 days
    type
    DRUG
  5. arm Group Labels
    1. histotype-tailored chemotherapy according to the histotype
    name
    etoposide 150 mg/m2/day (days 1, 2, 3) and ifosfamide 3g/m2/day (days 1, 2, 3)
    type
    DRUG
  6. arm Group Labels
    1. histotype-tailored chemotherapy according to the histotype
    name
    gemcitabine 1800 mg/m2 (day 1) and dacarbazine 500 mg/m2 (day 1)
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
550
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. measure
    To validate the response to preoperative chemotherapy (both radiological and pathological) as a surrogate endpoint by showing that disease free survival and overall survival depend on response status and are independent of the treatment arm.
    time Frame
    5 years
primary Outcomes
  1. measure
    To compare the effect on disease-free survival of full-dose standard chemotherapy with histotype-tailored chemotherapy within the context of an integrated strategy for high risk soft tissue sarcomas typical of the adult.
    time Frame
    5 years
secondary Outcomes
  1. measure
    1:overall survival 2:response in the whole population 3:response by RECIST and Choi in each different histotype 4:pathological response 5:feasibility of integration of preoperative chemotherapy with preoperative local-regional treatments 6:PET re
    time Frame
    5 years
Full study description
brief Summary
This is a randomized Phase III clinical trial in the setting of localized high-risk soft tissue sarcomas (STS). This study will compare a standard neoadjuvant chemotherapy with epirubicin plus ifosfamide versus a histology-driven chemotherapy, i.e. a chemotherapy tailored to the specific histology within the family of adult STS. Chemotherapy will be administered for 3 cycles. There will be five histological groups (representing 80% of STS), as follows: leiomyosarcoma, myxoid liposarcoma with hypercellularity (round cell MLPS), synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST) and undifferentiated pleomorphic sarcoma. The histology-driven chemotherapy for these groups will be, respectively, gemcitabine plus dacarbazine, trabectedin, high-dose ifosfamide, ifosfamide plus etoposide, gemcitabine plus docetaxel. Other histological groups will also be included and registered, but treated only by standard chemotherapy. Patients who have already undergone definitive surgery will receive treatment post-operatively and patients needing a re-excision after inadequate surgery will be treated as patients in the two groups, but of course will not be evaluable for response. A centralized pathological review will be performed. Radiological response will be evaluated according to RECIST and to Choi criteria. Pathological response will also be recorded. The endpoint will be disease-free survival (DFS) and, secondarily, overall survival (OS) of patients receiving standard chemotherapy versus those receiving histotype-tailored chemotherapy. Additional aims will be to compare the probability of response of standard vs histotype-tailored chemotherapy and to determine the radiological and pathological response with standard chemotherapy vs tailored chemotherapy in each different histological group. Another aim will be to validate the response (both radiological and pathological) to preoperative chemotherapy as a surrogate endpoint for DFS and OS. Three hundred patients will be randomized over a 3-years period, from a pool of 400-450 registered patients. Translational research will be performed. Areas of research will include identification and validation of the potential predictive markers for each histological subgroups. The study is designed to verify the statistical hypothesis that histotype-tailored approach is associated, overall, with a 30% reduction in the hazard of relapse. However, in each different histological group, the effect of histotype-tailored chemotherapy, as compared to standard chemotherapy, can be different. To address this weakness an orthogonal study of response to chemotherapy as a surrogate of DFS and OS has been introduced into the trial. This study intends to extensively investigate the response (radiological and pathological) to preoperative chemotherapy and to validate it as a surrogate endpoint by showing that it correlates with disease free survival and overall survival.
Source references
references
  1. citation
    Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay JY, Tendero O, Diaz Beveridge R, Ferraresi V, Lugowska I, Pizzamiglio S, Verderio P, Fontana V, Donati DM, Palassini E, Sanfilippo R, Bianchi G, Bertuzzi A, Morosi C, Pasquali S, Stacchiotti S, Bague S, Coindre JM, Miceli R, Dei Tos AP, Casali PG. Neoadjuvant Chemotherapy in High-Grade Myxoid Liposarcoma: Results of the Expanded Cohort of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish Sarcoma Groups (PSG). J Clin Oncol. 2024 Mar 10;42(8):898-906. doi: 10.1200/JCO.23.00908. Epub 2024 Jan 17.
    pmid
    38232337
    type
    DERIVED
  2. citation
    Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay JY, Tendero O, Diaz Beveridge R, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Braglia L, Donati DM, Palassini E, Bianchi G, Marrari A, Morosi C, Stacchiotti S, Bague S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020 Jul 1;38(19):2178-2186. doi: 10.1200/JCO.19.03289. Epub 2020 May 18.
    pmid
    32421444
    type
    DERIVED
  3. citation
    Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bague S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. doi: 10.1016/S1470-2045(17)30334-0. Epub 2017 May 9.
    pmid
    28499583
    type
    DERIVED
  4. citation
    Gronchi A, Stacchiotti S, Verderio P, Ferrari S, Martin Broto J, Lopez-Pousa A, Llombart-Bosch A, Dei Tos AP, Collini P, Jurado JC, De Paoli A, Donati DM, Poveda A, Quagliuolo V, Comandone A, Grignani G, Morosi C, Messina A, De Sanctis R, Bottelli S, Palassini E, Casali PG, Picci P. Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Ann Oncol. 2016 Dec;27(12):2283-2288. doi: 10.1093/annonc/mdw430. Epub 2016 Oct 11.
    pmid
    27733375
    type
    DERIVED
  5. citation
    Palassini E, Ferrari S, Verderio P, De Paoli A, Martin Broto J, Quagliuolo V, Comandone A, Sangalli C, Palmerini E, Lopez-Pousa A, De Sanctis R, Bottelli S, Libertini M, Picci P, Casali PG, Gronchi A. Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Espanol de Investigacion en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide. J Clin Oncol. 2015 Nov 1;33(31):3628-34. doi: 10.1200/JCO.2015.62.9394. Epub 2015 Sep 8.
    pmid
    26351345
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-469e36d93afd00f9ce7b
      requested nct id
      NCT01710176
      primary nct id
      NCT01710176
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      9465d9a72734c9bd3e3db859fe4c8f227bb30b5f70dc6864a0d40359b8ea84d3
      payload sha256
      a4d25aa351519c485758bcd376b34229abfb77a079fc2de804d179d92c79ed84
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-469e36d93afd00f9ce7b
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT01710176
      occurrences
      1. context exact
        histotype-tailored chemotherapy vs. standard chemotherapy):</p> <div class="pdq-content-list"><ol id="_2269"><li>The phase III <a href="/clinicaltrials/NCT01710176">ISG-STS1001</a> study (NCT01710176) enrolled 164 patients with high-risk features (grade 3 tumor or grade 2 tumor with more than 50% necrosis, size &#8805;5 c
        end
        109472
        exact text
        NCT01710176
        start
        109461
      2. context exact
        standard chemotherapy):</p> <div class="pdq-content-list"><ol id="_2269"><li>The phase III <a href="/clinicaltrials/NCT01710176">ISG-STS1001</a> study (NCT01710176) enrolled 164 patients with high-risk features (grade 3 tumor or grade 2 tumor with more than 50% necrosis, size &#8805;5 cm, deep location).[<a href="#cit/sec
        end
        109508
        exact text
        NCT01710176
        start
        109497
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/fc630f597981bfeac3.html
      source file sha256
      9465d9a72734c9bd3e3db859fe4c8f227bb30b5f70dc6864a0d40359b8ea84d3
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:19.112058+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      7192ca8ed54c92ff6b85c1b874bce0b65c4fd0808e206dcdb389df3def53014a
      source title
      Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: February 21, 2025
        datetime
        2025-02-21T12:00:00Z
        display
        February 21, 2025

    Preserved source evidence · Not medical advice