NCT00541840

Phase I-II Trial of Sorafenib in Combination With Ifosfamide in Soft Tissue Sarcoma

Phase I-II, Not-Randomized, Multicenter Clinical Trial to Evaluate Safety and Efficacy of Sorafenib (BAY-43-9006) in Combination With Ifosfamide in Soft Tissue Sarcoma.

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Grupo Espanol de Investigacion en Sarcomas · Academic / Other
• Sex: All
• Age: 18 Years – 72 Years
• Healthy volunteers: Not accepted

Summary

Soft tissue sarcomas (STS) are an uncommon group of malignant tumors of mesenchymal origin. For most advanced STS types, chemotherapy is currently the only available treatment. Unfortunately, a very limited number of useful drugs are active against this disease. Doxorubicin is widely considered the standard first-line treatment. Ifosfamide has also a well-established activity (1,2) and is often administered either associated with Doxorubicin or alone as a second-line chemotherapy treatment. Other drugs such as DTIC, Gemcitabine and Temozolomide showed modest activity as a second-line agents (3,4). Thus, there is a necessity to identify new agents with activity to improve therapy for patients with advanced STS. In some studies, most STS showed VEGF expression, and elevated serum VEGF levels were found to correlate with higher histologic tumor grade (5,6). Additionally, inhibition of VEGFR was associated with tumor activity in preclinical models of sarcoma (7,8). For these reasons, inhibition of VEGFR seems to be a reasonable approach to explore in the treatment of STS. Sorafenib (BAY 43-9006) is an orally available, small molecule multi-kinase inhibitor of VEGFR, PDGFR and RAF with demonstrated activity in the treatment of renal cell cancer (9). Preclinical studies suggest that the combination of Sorafenib with cytotoxic agents results in additive anti-tumor activity (10), initiating justification for combination studies. A recent trial, however, reported an unexpected incidence of cardiac toxicity in patients with STS treated with Bevacizumab, a monoclonal antibody that binds VEGF, in combination with Doxorubicin (11). This finding suggest that the possibility of potentiation of the cardiotoxicity of Doxorubicin when inhibiting the VEGF pathway cannot be ruled out. The association of Sorafenib with Ifosfamide, the other established active agent against STS, could improve the efficacy of single-agent Ifosfamide minimizing the risk of cardiac toxicity .

Conditions

• Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Sorafenib	Phase I: Level 1: Sorafenib 200 mg bid, orally Ifosfamide 2,0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Level 2: Sorafenib 400 mg bid, orally Ifosfamide 2.00 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Level 3 : Sorafenib 400mg bid, orally Ifosfamide 2.5 g/m2 , intravenously , over 4 hours , on 3 consecutive days . Mesna 500mg/m2,iv,at 0,4 and 8 hours after ifosfamide administration . Level 4 : Sorafenib 400 mg bid, orally Ifosfamide 3.0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 600 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Phase II: Sorafenib and Ifosfamide administered at the doses recommended in phase I until progression or unacceptable toxicity.

Timeline

• Start date: 2007-10-01
• Primary completion: 2009-04-01
• Completion: 2010-04-01
• First posted: 2007-10-10
• Last updated: 2008-05-12

Locations

1 site across 1 country: Spain