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Trial record 1 of 1 for:    NCT01710176
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Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy

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ClinicalTrials.gov Identifier: NCT01710176
Recruitment Status : Active, not recruiting
First Posted : October 19, 2012
Last Update Posted : July 28, 2020
Sponsor:
Collaborators:
French Sarcoma Group
Grupo Espanol de Investigacion en Sarcomas
Information provided by (Responsible Party):
Italian Sarcoma Group

Tracking Information
First Submitted Date  ICMJE October 17, 2012
First Posted Date  ICMJE October 19, 2012
Last Update Posted Date July 28, 2020
Actual Study Start Date  ICMJE June 1, 2011
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2012)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2012)
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
Current Other Pre-specified Outcome Measures
 (submitted: March 26, 2015)
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 ]
Original Other Pre-specified Outcome Measures
 (submitted: October 18, 2012)
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.
 
Descriptive Information
Brief Title  ICMJE Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy
Official Title  ICMJE Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Localized High-risk Soft Tissue Sarcomas of the Extremities and Trunk Wall in Adults
Intervention  ICMJE
  • Drug: epirubicin 60 mg/m2/day (days 1, 2) and ifosfamide 3 g/m2/day (days 1, 2, 3)
  • Drug: gemcitabine 900 mg/m2 (days 1 and 8) and docetaxel 75 mg/m2 (day 8)
  • Drug: trabectedin 1.3 mg/m2
  • Drug: high-dose ifosfamide 14 g/m2, given in in 14 days
  • Drug: etoposide 150 mg/m2/day (days 1, 2, 3) and ifosfamide 3g/m2/day (days 1, 2, 3)
  • Drug: gemcitabine 1800 mg/m2 (day 1) and dacarbazine 500 mg/m2 (day 1)
Study Arms  ICMJE
  • Active Comparator: standard chemotherapy with full-dose epirubicin + ifosfamide
    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: Drug: epirubicin 60 mg/m2/day (days 1, 2) and ifosfamide 3 g/m2/day (days 1, 2, 3)
  • Experimental: histotype-tailored chemotherapy according to the histotype
    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
    Interventions:
    • Drug: gemcitabine 900 mg/m2 (days 1 and 8) and docetaxel 75 mg/m2 (day 8)
    • Drug: trabectedin 1.3 mg/m2
    • Drug: high-dose ifosfamide 14 g/m2, given in in 14 days
    • Drug: etoposide 150 mg/m2/day (days 1, 2, 3) and ifosfamide 3g/m2/day (days 1, 2, 3)
    • Drug: gemcitabine 1800 mg/m2 (day 1) and dacarbazine 500 mg/m2 (day 1)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 9, 2019)
550
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2012)
350
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01710176
Other Study ID Numbers  ICMJE ISG-STS 10-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Italian Sarcoma Group
Study Sponsor  ICMJE Italian Sarcoma Group
Collaborators  ICMJE
  • French Sarcoma Group
  • Grupo Espanol de Investigacion en Sarcomas
Investigators  ICMJE Not Provided
PRS Account Italian Sarcoma Group
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP