Dose-Escalation Study of TH-302 in Combination With Sunitinib to Treat Patients With Advanced Renal Cell Carcinoma and Gastrointestinal Stromal Tumors (TH-CR-410)

Dose-Escalation Study of TH-302 in Combination With Sunitinib to Treat Patients With Advanced Renal Cell Carcinoma and Gastrointestinal Stromal Tumors (TH-CR-410)

Gastrointestinal Stromal Tumor

Unknown

1

Start Date 06/01/2011

Age of Trial (yrs) 12.9

Gleevec-resistant

KIT/PDGFRA inhibitor + chemotherapy released in tumors with hypoxia

Block KIT + traditional chemotherapy

Specifically GIST plus other cancers

TH-CR-410

Threshold Pharmaceuticals

Esther Chu 650-474-8281 echu@Thresholdpharm.com

Oral Intravenous

Patients with either advanced renal cell carcinoma or GIST that is resistant to imatinib (or intolerant to imatinib) are eligible for this trial. GIST patients are only eligible for the dose escalation phase of the trial.
Sunitinib (Sutent) is approved as a single agent for imatinib-resistant or intolerant GIST. This phase I trial will test the combination of sunitinib and TH-302.
TH-302 is a pro-drug that selectively targets tumors cells with low oxygen content (hypoxia). TH-302 has been designed to be selectively activated within these hypoxic cells, killing them as well as those in close proximity via a bystander effect.
The primary objectives of this trial are:
1. To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.

Dose expansion:

To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D
To assess the safety of TH-302 in combination with sunitinib and determine a recommended Phase 2 dose of the combination.

The secondary objectives are:

Dose expansion:

1. To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by stable disease or better rate, duration of response and overall survival in subjects with advanced RCC treated at the RP2D.

The exploratory objective is:

1. To explore the association of serum hypoxia biomarkers with efficacy endpoints.

See the NCT link above for complete trial details.