1461TiP - Multicenter phase 3 study of efficacy and safety of aldoxorubicin versus investigator's choice for relapsed/refractory soft tissue sarcomas

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Soft Tissue Sarcomas
Presenter Sant Chawla
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors S.P. Chawla1, K. Sankhala1, S. Wieland2, D. Levitt3
  • 1Med. Oncology, Sarcoma Oncology Center, 90403 - Los Angeles/US
  • 2Clinical Operations, CytRx Corporation, 90049 - Los Angeles/US
  • 3Clinical Development, CytRx Corporation, 90049 - Los Angeles/US

Abstract

Background

Aldoxorubicin is a novel prodrug that covalently binds albumin in the circulation. Doxorubcin is cleaved in low pH environments, allowing administration of 3 1/2 to 4 fold higher doses than standard doxorubicin and 10-fold greater cumulative doses. Patients with metastatic or unresectable soft tissue sarcomas (STS) who have failed prior chemotherapies have a poor prognosis with progresson-free survival (PFS) of around 2-4.5 months and overall survival (OS) of 9-12 months. Several agents have been tested as palliative therapy with these patients including ifosfamide, gemcitabine/docetaxel, dacarbazine and pazopanib. Aldoxorubicin may improve upon the activity of these drugs.

Trial design

Phase 3 Open label 400 subjects with intermediate or high grade locally advanced or metastatic STS randomized 1:1 to either aldoxorubicin (A) (350 mg/m2 iv Day 1 every 3 weeks) or investigator's choice (IC) as comparator of any of these treatments: (i) dacarbazine (1000 mg/m2 iv Day 1 every 3 weeks); (ii) pazopanib 800 mg po (iii) gemcitbine (900 mg/m2 iv Days 1 & 8) plus docetaxel (100 mg/m2 iv Day 8) every 3 weeks; (iv) doxorubicin (75 mg/m2 iv Day 1 every 3 weeks); (v) ifosfamide (2 gm/m2 iv Days 1-4 every 3 weeks). The investigative site prespecifies 3 treatment regimens for which CytRx will supply the drugs. Treat to progression or unacceptable toxicity Major inclusions: histological confirmation of tumor type with tissue provided for central review; relapsed/refractory after >/= 1 course of chemotherapy; measurable tumor by RECIST 1.1; ECOG 0-2 Major exclusions:prior exposure to> 375 mg/m2 doxorubicin; inadequate tumor specimen; diagnosis of GIST, alveolar soft part, rhabdo, Ewing's, Kaposi's, osteo, extraskeletal myxoid chondro, dermatofbro, or clear cell sarcomas, or mixed mesodermal tumor; clinically significant cardiac disease, LFTs> 3x (no mets) or 5x (liver mets) normal; ANC<1000/mm3; platelets<100,000/mm3, Hgb<9 gm/dL. CT scans every 6 weeks to progression. Endpoints: Primary: PFS (5.1 months for A, 3 months for IC); Secondary: OS, ORR, PFS at 6 months, adverse events. Study sites in US, Canada, France, Italy, Spain, Netherlands, Denmark, Sweden, Hungary, Czech Republic, Poland, Israel, S. Korea, Australia, Argentina, Chile, Brazil. This Study has Special Protocol Assessment from the US FDA.

Disclosure

S. Wieland: CytRx Employee, Salary and Stock options; D. Levitt: CytRx Employee; Salary and Stock Options. All other authors have declared no conflicts of interest.