Redwood City, Calif — Threshold Pharmaceuticals, Inc, has announced that it has reached agreement with the FDA on a special protocol assessment (SPA) for a Phase 3 randomized trial of TH-302 in patients with sof-tissue sarcoma. This pivotal trial is expected to begin in the middle of 2011, and will enroll patients with metastatic or locally advanced unresectable soft tissue sarcoma who have not previously received chemotherapy outside the adjuvant or neoadjuvant setting. The trial is designed to evaluate the efficacy and safety of TH-302 in combination with doxorubicin, compared to doxorubicin alone.
A special protocol assessment is a written agreement with the FDA on the design and planned analysis for a clinical trial. It is intended to
form the basis for a marketing application and may only be changed through a written agreement between the sponsor and the FDA, or if the
FDA becomes aware of new public health concerns.
"With this SPA, we have reached agreement with the FDA on the key features of our Phase 3 trial design that will be necessary to support
the registration of TH-302," said Stewart Kroll, Threshold’s vice president, Biostatistics and Clinical Operations. "The proposed trial is designed to confirm the encouraging results that we have previously reported in our ongoing Phase 1/2 trial of soft tissue sarcoma patients
treated with TH-302 in combination with doxorubicin."
TH-302 has been investigated in over 400 patients with cancer as part of five clinical trials. The TH-302 clinical development program
includes an ongoing Phase 1/2 trial in patients with soft tissue sarcoma. As presented at the Connective Tissue Oncology Society meeting in November 2010, fifty-four patients had at least one evaluable post-treatment tumor assessment and 18 of 54 (33%) had a partial response. The median progression free survival was 6.4 months (95% confidence interval: 5.6 to 6.9 months). These data formed the basis for the proposed Phase 3 study of TH-302 and doxorubicin compared to doxorubicin, as covered by the SPA.
In addition, Threshold is pursuing additional clinical trials in patients with solid tumors as well as hematologic malignancies. TH-302 is currently being evaluated in a Phase 2 randomized, controlled combination trial in patients with metastatic or locally advanced pancreatic cancer as well as a Phase 1 open label, monotherapy trial in patients with advanced leukemias.
The Phase 3 trial will be a 450 patient, randomized, open-label, multi-center trial comparing two treatment regimens for patients with
metastatic and/or advanced unresectable soft tissue sarcoma who have not received prior doxorubicin. This trial is designed to demonstrate
the clinical benefit of TH-302 in combination with doxorubicin compared to doxorubicin alone based on a primary efficacy endpoint of overall
survival. The trial includes an interim analysis based on progression-free survival expected to occur about half-way into enrollment and an interim analysis based on overall survival expecte to occur at the end of enrollment. Patients will be randomized to receive TH-302 (300 mg/m2 on days 1 and 8 of a 21 day cycle) in addition to the standard dosing schedule of doxorubicin (75 mg/m2 on day 1 of the 21 day cycle) compared to doxorubicin alone.
Sarcomas are a group of aggressive cancers of connective tissue of the body for which there are currently limited treatment options. Soft
tissue sarcomas are treated with surgery, chemotherapy and radiation. Usually a combination of these modalities offers the best chance to
treat the disease successfully. Doxorubicin and ifosfamide are the most commonly used chemotherapeutic agents in patients with advanced soft tissue sarcoma, but response rates are generally low and toxicity can be significant. The American Cancer Society estimates that 10,520
people were diagnosed with a soft tissue sarcoma in the United States in 2010, and approximately 3,920 people died from the disease.
SOURCE: Threshold Pharmaceuticals