Gemcitabine and Docetaxel With or Without Bevacizumab (Onbevzi) for Soft Tissue Sarcoma

Phase II, Randomized Trial of Gemcitabine and Docetaxel With or Without Bevacizumab (Onbevzi) for Previously Treated Soft Tissue Sarcoma

Arm1- bevacizumab (Onbevzi) at a dose of 15 mg/kg administered as a 30-minute intravenous infusion on Day 1 of each 21-day cycle, followed by intravenous infusion of gemcitabine and docetaxel in sequence. On Day 8 of each cycle, gemcitabine and docetaxel will be administered as a 60-minute intravenous infusion.

Arm2- On Day 1 of each 21-day cycle, gemcitabine will be administered first, followed by docetaxel as an intravenous infusion. On Day 8, gemcitabine and docetaxel will be administered as intravenous infusions.

Inclusion Criteria:

1. Histologically confirmed advanced leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), liposarcoma, or angiosarcoma with 1-2 prior chemotherapy

   : neoadjuvnat or adjuvant chemotherapy is counted as one regimen

2. Age ≥19 years, <80 years

3. ECOG performance status of 0-1

4. Has at least 1 measurable lesion (as defined by RECIST v1.1).

5. Has adequate organ function defined by the following criteria:

   • Hb ≥ 9.0 g/dL
   • Absolute neutrophil count (ANC) ≥ 1500 /µL
   • Platelet ≥ 75,000/ µL
   • Total Bilirubin: ≤ 1.5 × UNL (upper normal limit) (≤ 2 × UNL in patients with liver metastasis)
   • Serum Creatinine: ≥ 50 mL/min
   • AST(SGOT)/ALT(SGPT): ≤ 3.0 × UNL or ≤ 5.0 × UNL (in patients with liver metastasis)
   • Alkaline Phosphatase (ALP): ≤ 3.0 × UNL or ≤ 5.0 × UNL (in patients with liver or bone metastasis)

6. Female patient of childbearing potential has a negative serum or urine pregnancy test for β-hCG

7. Able to provide written informed consent and comply with the protocol requirements

Exclusion Criteria:

1. Patient who has had chemotherapy, radiotherapy, or biological therapy within 2 weeks prior to entering the study
2. More than 3 prior cytotoxic agents
3. previously received treatment with bevacizumab, gemcitabine, or docetaxel
4. Unresolved toxicities from prior anticancer therapy ≥ Grade 2 according to NCI CTCAE, excluding alopecia, vitiligo, and laboratory abnormalities defined in the inclusion criteria
5. Major surgery within 28 days prior to randomization.
6. Active or prior documented autoimmune or inflammatory disorders
7. Unstable cardiovascular disease
8. Has an active infection requiring parenteral treatment
9. History of another primary malignancy
10. Uncontrolled or active CNS metastasis and/or carcinomatous meningitis
11. Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
12. Pre-existing interstitial lung disease (ILD)