This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.
Standard arm: * Large en-bloc curative-intent surgery within 4 weeks following randomization- Experimental arm Experimental arm: * 3 cycles of neoadjuvant chemotherapy starting within 2 weeks following randomization: * High grade LPS: ADM (doxorubicin) 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m3 Q3 weeks. * LMS: ADM 75 mg/m2 + DTIC (dacarbazine) 1 g/m2 Q3 weeks * re-assessment of operability * curative-intent surgery within 3-6 weeks of last cycle of chemotherapy
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
Large en-bloc curative-intent surgery
* High grade LPS: ADM 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m2 Q3 weeks * LMS: ADM 75 mg/m2 + DTIC 1g/m2 Q3 weeks Note: the recommended dose of Doxorubicin (or Epirubicin) can be modified according to national/institutional guidelines, given that the minimal threshold must be Doxorubicin 60 mg/m2 per cycle (or the equivalent Epirubicin 95 mg/m2 per cycle); the recommended dose of Ifosfamide can be modified according to national/institutional guidelines, given that the minimal threshold must be 7.5 g/m2 per cycle; the recommended dose of Dacarbazine can be modified according to national/institutional guidelines, given that the minimal threshold must be 900 mg/m2 per cycle. The schedule of administration of above chemotherapies can be modified according to national/institutional guidelines provided that the minimal threshold of doses, and the treatment periods with chemotherapies remain the same.
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
RECRUITINGCity of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGUC Irvine Health/Chao Family Comprehensive Ca Ctr
Orange, California, United States
RECRUITINGUCHealth University of Colorado Hospital
Aurora, Colorado, United States
Disease free survival
Disease free survival will be measured from the date of randomization (as reference) to the date of recurrence or death, whichever occurs first.
Time frame: 7 years from first patient in
Overall survival (OS)
OS will be measured from the date of randomization to the date of death, whatever the cause. Alive patients will be censored at the date of last follow-up.
Time frame: 8 years from first patient in
Recurrence free survival
Recurrence free survival will be measured in patients who were successfully operated (R0/R1 resection) from the date of surgery (as reference) to the date of recurrence (local or distant) or death, whichever occurs first. Patients without one of these events will be censored at the date of last follow-up.
Time frame: 8 years from first patient in
Distant metastases free survival
Distant metastases free survival will be from the date of randomization (as reference) to the date of distant metastases or death (whatever the cause), whichever occurs first. Patients without any of these events will be censored at the date of last follow-up.
Time frame: 8 years from first patient in
Cumulative incidence of local recurrences
Cumulative incidence of local recurrences will be measured from the date of randomization (as reference) to the date of local recurrence.
Time frame: 8 years from first patient in
Cumulative incidence of distant metastases
Cumulative incidence of distant metastases will be measured from the date of randomization to the date of occurrence of distant metastases.
Time frame: 8 years from first patient in
Radiological response to neoadjuvant chemotherapy according to RECIST
For patients receiving neo-adjuvant chemotherapy, the radiological response will be assessed using RECIST 1.1 by comparison of the baseline and preoperative imaging.
Time frame: 8 years from first patient in
Radiological response to neoadjuvant chemotherapy according to CHOI
For patients receiving neo-adjuvant chemotherapy, the radiological response will be also assessed using Choi criteria by comparison of the baseline and preoperative imaging.
Time frame: 8 years from first patient in
Pathological response
Response evaluation will be done according to the EORTC response score.
Time frame: 8 years from first patient in
Safety and toxicity of neoadjuvant chemotherapy
Safety and toxicity of neoadjuvant chemotherapy will be evaluated and graded using CTCAE V5.0.
Time frame: 8 years from first patient in
Perioperative complications
Perioperative complications will be evaluated with the Dindo scale for the events related to the surgery and CTCAE V5.0 will be used for all other events.
Time frame: 8 years from first patient in
Late complications
Late complications (after the 60th day following the surgery) will be evaluated and graded according to the CTCAE version 5.0.
Time frame: 8 years from first patient in
Health-Related Quality of life (EORTC QLQ-C30 + Item list from QLQ-STO22)
Health-Related Quality of life assessment will be based on the EORTC QLQ C30 questionnaire version 3.0, with additional questions from the QLQ-STO22 module.
Time frame: 8 years from first patient in
Health utility, calculated from the collected patient-reported HRQoL data and patient demographics economics.
he EORTC QLQ C30 data will be mapped to health utility values using an established indirect mapping approach.
Time frame: 8 years from first patient in
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Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care Center - Guiford
Guilford, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care Ctr at Saint Francis
Hartford, Connecticut, United States
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