Phase III Study Comparing Trabectedin (T) Versus T Plus tTF-NGR to Entrap T Inside the Tumor in Patients With Metastatic and/or Refractory Soft Tissue Sarcoma (STS)
In this phase III open label, controlled clinical trial patients with unresectable or metastatic soft-tissue sarcoma after failure of anthracycline-containing first line therapy or with contraindications to these drugs and CD13 positivity in central histology (grade \>/= 1+) are treated to evaluate whether tTF-NGR in combination with standard trabectedin chemotherapy prolongs progression-free survival (according to iRECIST), as compared with trabectedin alone. Further objectives are to evaluate the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy with respect to the response rate and overall survival as well as to assess the safety profile of tTF-NGR combined with trabectedin. Before the randomized phase III part of the study, there was a safety run-in part. The final dose of tTF-NGR established as safe in this safety run-in part is 0.5 mg/m2 per day for 2 consecutive days following each trabectedin infusion and is used for the randomized (parallel 1:1; Arm 1: standard trabectedin, Arm 2: standard trabectedin plus tTF-NGR) phase III part of this trail. . Further dose modification for tTF-NGR is possible.
• Patients of all genders (female, male, diverse), with no restriction regarding ethnic or religious background age 18 - 75 years.
• Patients with advanced or metastatic soft-tissue sarcoma after failure of anthracycline-containing first line therapy (or anthracycline-containing adjuvant therapy within 12 months before entry on study) or with contraindications to these drugs
• Patients must have histological evidence of high-grade advanced unresectable or metastatic soft tissue sarcoma (grade 2 - 3) according to the FNCLCC grading system. The following tumor types are included:
‣ Dedifferentiated liposarcoma
⁃ Myxoid liposarcoma (high grade)
⁃ Pleomorphic liposarcoma
⁃ Adult fibrosarcoma
⁃ Myxofibrosarcoma (high-grade)
⁃ Leiomyosarcoma
⁃ Rhabdomyosarcoma (alveolar, pleomorphic)
⁃ Angiosarcoma
⁃ Synovial sarcoma
⁃ Undifferentiated sarcoma
• Tumor types not listed above may be included upon communication with Coordinating Investigator.
• The following tumor types will not be included:
⁃ Gastrointestinal stromal tumors (GIST)
⁃ Epitheloid sarcoma
⁃ Alveolar soft part sarcoma
⁃ Desmoplastic small round cell tumor
⁃ Chondrosarcoma
⁃ Osteosarcoma
⁃ Ewing sarcoma (including CIC-rearranged sarcoma and Sarcoma with BCOR alterations)
• CD13 positivity with a score of ≥ 1 (20) by central pathology (GDI Münster)
• Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria 1.1. Other adequate imaging procedures such as MRI are allowed. This lesion should not have been irradiated during previous treatments
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• No contraindications for trabectedin (see attachment)
• Negative serum pregnancy test for females of childbearing potential\* within 14 days of starting treatment
⁃ Informed consent signed and dated to participate in the study
⁃ Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures
∙ Women of childbearing potential (WOCBP) must be using, from the screening to 3 months following the last trabectedin (Arm 1) or the last last study drug (Arm 2) administration, highly effective contraception methods, as defined by the Recommendations for contraception and pregnancy testing in clinical trials issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesteron-only or combined (estrogen- and progesteron-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. Pregnancy test will be repeated monthly. For men contraception methods should be performed for 5 months after the last application of trabectedin (Arm1) or study drug (Arm 2).Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)