Introduction/Background*As there are only a few therapy options for advanced or recurrent leiomyosarcoma (LMS) and Carcinosarcomas (CS), new effective drug combinations with an acceptable toxicity profile are urgently needed.

Pazopanib is an orally available second-generation multi targeted tyrosine kinase inhibitor (TKI), targeting among others VEGFR, PFGG and c-kitand is approved in soft tissue sarcomas.

A phase I study evaluated the combination of pazopanib and gemcitabine and showed an acceptable toxicity profile. We aim to test the activity of the combination therapy in patients with LMS in a randomized setting and to describe the activity in CS.

Methodology The PazoDoble study is a prospective, randomized, open-label, multicentre phase II trial. Patients with relapsed or metastatic uterine LMS or uterine CS are eligible for participation. LMS are randomised in a 1:1 fashion into two treatment arms. A: pazopanib 800 mg p.o./d plus gemcitabine 1000mg/m2 i.v. over 30 min d1 und d8 q3w or B: pazopanib 800 mg p.o./d. Uterine CS will be enrolled only in Arm A. Duration of therapy will be maximum 18 months or until progression, death or unacceptable toxicity. Primary Endpoints are the six month PFS and clinical progression; Secondary endpoints are the objective response rate, duration of response, time to progression, OS, toxicity and tolerability and quality of life. A previousatment with doxorubicin or any contraindications against doxorubicin and an ECOG of 0 or 1 are mandatory. Clinical and imaging follow-up are scheduled every three month until disease progression or death.

Enrolment was started in October 2019 at nine sites. Until now, 12 Patients are enrolled (5 CS and 7 LMS). We aim to include 87 patients with LMS and 20 with CS. The primary endpoint will be analysed as the ratio of the number of patients showing no progress after 6 month divided by the number of evaluable patients. A drop-out rate of 5% was assumed.

Conclusion*In the clinical setting of advanced and recurrent LMS and CS there are no well-evaluated therapies available. This trial is clinically highly relevant and offers opportunity for patients to receive promising therapy.