Trabectedin in Combination with the New Active Ingredient tTF-NGR Compared with Trabectedin Alone in Patients with Advanced or Recurrent Soft Tissue Sarcoma (TRABTRAP)

Soft tissue sarcomas are a group of rare malignant tumors of soft tissue, such as muscle, fat, or connective tissue. If the disease is advanced or has spread (metastasized) to other parts of the body, and if it has progressed further after initial treatment with anthracyclines (or if such treatment is not an option), treatment options are limited. In this situation, the active ingredient trabectedin, among others, is used as the standard treatment. Trabectedin is a chemotherapeutic agent that inhibits the growth of cancer cells and is administered as an intravenous infusion. tTF-NGR is a new investigational drug that specifically binds to the surface marker CD13 on tumor cells and in the walls of tumor blood vessels and, by selectively triggering small blood clots (microthrombi) in tumor vessels, thereby cutting off the tumor’s blood supply and depriving the cancer cells of their nutrient supply. tTF-NGR is also administered as an intravenous infusion. The goal of this Phase 3 trial is to investigate whether the addition of the new active ingredient tTF-NGR to standard therapy with trabectedin can delay disease progression longer than trabectedin alone (progression-free survival, PFS). To this end, patients will be randomly assigned to two groups. The treatment arm receives trabectedin in addition to tTF-NGR. The control arm receives standard therapy with trabectedin alone. Trabectedin is administered as an infusion via a central venous access (e.g., a port) over 24 hours. Treatment takes place on Day 1 of a treatment cycle. The active ingredient tTF-NGR is also administered as an infusion over approximately one hour. It is given on Days 2 and 3 of each treatment cycle, following the trabectedin treatment on each occasion. There is a break of approximately one hour between the end of the trabectedin infusion and the start of tTF-NGR. A treatment cycle lasts 22 days. Treatment is continued as long as the disease does not progress further and there are no reasons against continuing treatment. The study is open-label (unblinded), meaning that both the study physicians and the patients know which treatment is being administered. The follow-up period is set at 100 months (approximately 8 years). Patients between the ages of 18 and 75 with advanced, inoperable, or metastatic soft-tissue sarcoma of high malignancy grade (Grade 2–3), whose tumor cells express CD13 (confirmed CD13 positivity according to central pathological review at the Gerhard Domagk Institute for Pathology, Münster). 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, and undifferentiated sarcoma. A prerequisite is that the disease has progressed further following initial treatment with anthracyclines or that such treatment is not feasible.