Solid Tumors
410 Trial: Phase 1 trial evaluating the safety of TH-302 in combination with sunitinib in patients with advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST). Enrollment is currently open.
406 Trial: Phase 3 multi-center, randomized, controlled clinical trial of TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. The Company plans to commence this trial in the third quarter of 2011. This trial is not yet open to enrollment.
404 Trial: Phase 2 multi-center, randomized, controlled, crossover clinical trial of TH-302 in combination with gemcitabine in patients with first line pancreatic cancer. Enrollment has been completed and is currently closed.
403 Trial: Phase 1/2 trial evaluating the safety of TH-302 in combination with doxorubicin in patients with soft tissue sarcoma. Enrollment has been completed and is currently closed.
402 Trial: Phase 1/2 trial evaluating the safety of TH-302 in various solid tumors in combination with several approved chemotherapeutic agents. Primary tumor types investigated: advanced pancreatic cancer, castrate-resistant prostate cancer and non-small cell lung cancer. Enrollment has been completed and is currently closed.
401 Trial: Phase 1 study evaluating the safety of TH-302 as a monotherapy in various solid tumors. Enrollment has been completed and is currently closed.
Hematologic Malignancies
407 Trial: Phase 1 single-center, open-label clinical trial of TH-302 in patients with advanced leukemias. Enrollment is currently open at the MD Anderson Cancer Center in Houston, TX.
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For additional information about Threshold clinical trials, please contact the clinical trials group at 1-650-474-8222 or email us at clinicaltrials@thresholdpharm.com.
Disclosure of Risks
Please note that the safety and effectiveness of this product have not yet been established. As with other anti-cancer agents, this investigational product may not benefit you and may cause side effects. These side effects could be severe or even life threatening. There may be side effects that are not known or predictable at this time, but that may occur at the time of treatment or later. You should discuss these risks with your physician or a study doctor.
410 Trial – Renal Cell Carcinoma and Gastrointestinal Stromal Tumors
This is a Phase 1 dose escalation trial that is evaluating the efficacy and safety of TH-302 given in combination with sunitinib in patients with RCC or GIST. Approximately 12-24 patients will be enrolled in the dose escalation portion of this study. The initial dose of TH-302 will be 240 mg/m2. Up to six patients with RCC or GIST per dose level can participate in the dose escalation portion of the study. The highest dose level will be 575 mg/m2. Once the MTD has been reached, another 10 patients with advanced RCC will be enrolled. The primary endpoint for the dose escalation is to determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. The primary endpoints for the dose expansion portion of the study is to make a preliminary assessment of the safety and efficacy of TH-302 in combination with sunitinib as determined by response rate (RR) and progression-free survival (PFS) in patients with advanced RCC. The secondary efficacy endpoints are stable disease or better rate, duration of response and overall survival in patients with advanced RCC. Exploratory endpoints are to explore the association between serum hypoxia biomarkers with efficacy endpoints. Tumor response will be evaluated at baseline an every twelve weeks using RECIST.
TH-302 is being administered intravenously over approximately 30-60 minutes on Days 8, 15 and 22 of a 42 day cycle. Sunitinib is being given on Days 1-28 of a 42 day cycle. Patients over the age of 18 and have advanced RCC or GIST are eligible for this trial.
407 Trial – Advanced Leukemias
This is a Phase 1 dose escalation trial that is evaluating the safety of TH-302 in patients with advanced leukemias. Approximately 40 patients will be enrolled in the dose escalation portion of this study. The initial dose of TH-302 was 120 mg/m2. Up to six patients with advanced leukemias per dose level can participate in the dose escalation portion of the study. Once the MTD has been reached, another 10 patients with advanced leukemias will be enrolled. The primary endpoint for the dose escalation is to determine the MTD and DLT(s) of TH-302. The secondary endpoints are to determine the clinical activity of TH-302 and to evaluate the PK of TH-302 and Br-IPM. Exploratory endpoints are to determine the extent of hypoxia in the bone marrow of patients with advanced leukemia and to explore the association between serum hypoxia biomarkers with efficacy endpoints. TH-302 is being administered intravenously over approximately 30-60 minutes on Days 1-5 of every 21 day cycle. Patients over the age of 18 and have relapsed or refractory leukemias for which no standard therapy options are anticipated to result in a durable remission are eligible for this trial.
406 Trial – Soft Tissue Sarcoma
This Phase 3, multi-center, randomized, open-label study is designed to evaluate the efficacy and safety of TH-302 plus doxorubicin as compared with doxorubicin. Overall 450 subjects at least 15 years of age with unresectable locally advanced or metastatic soft tissue sarcoma previously not treated with chemotherapy (neoadjuvant and adjuvant chemotherapy permitted) will be enrolled at various sites in the US and internationally. The primary objectives of the trial are to compare overall survival and to assess the safety of TH-302 in combination with doxorubicin. The secondary efficacy endpoints are progression-free survival (PFS) at three months and at six months, response rate (RR), change in ECOG performance status and event-free survival (EFS). Tumor response will be evaluated at baseline an every six weeks using the Response Evaluation Criteria in Solid Tumors (RECIST). Patients with soft tissue sarcoma for whom monotherapy with doxorubicin is considered standard therapy are eligible for this trial. Patients will be randomized equally into one of two cohorts: TH-302 plus doxorubicin or doxorubicin alone. Patients on the combination arm who successfully complete one treatment of six cycles without evidence of significant treatment-related toxicity or progressive disease may continue to receive TH-302 alone. TH-302 is being administered intravenously over approximately 30-60 minutes on Days 1 and 8 of a 21 day cycle. Doxorubicin will be given intravenously on Day 1 as a bolus administration or as a continuous administration over 2 to 4 days of each 21 day cycle.
404 Trial – Advanced Pancreatic Cancer
This is a multi-center, randomized, controlled, crossover Phase 2 clinical trial of TH-302 in combination with gemcitabine in patients with first line pancreatic cancer. Approximately 200 patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma are planned to enroll in the clinical trial at various sites in the United States. The primary endpoint of the trial is progression free survival. The secondary endpoints are overall response rate (ORR), overall survival (OS), event-free survival (EFS), CA 19-9 response rate as well as various safety parameters. Tumor response will be evaluated at baseline and every eight weeks using the Response Evaluation Criteria In Solid Tumors (RECIST). Patients for whom monotherapy with gemcitabine is considered standard therapy are eligible for the trial. Patients will be randomized equally into one of three cohorts: TH-302 at a dose of 240 mg/m2 plus gemcitabine or TH-302 at a dose of 340 mg/m2 plus gemcitabine or gemcitabine alone. Patients who successfully complete one treatment of six cycles without evidence of significant treatment-related toxicity or progressive disease may continue to receive treatment. If a patient's cancer progresses while on gemcitabine alone, the patient may crossover into one of the TH-302 plus gemcitabine cohorts. Enrollment has been completed and is currently closed. Top line data will be available around the end of 2011.
403 Trial – Soft Tissue Sarcoma
This is a Phase 1/2 dose escalation trial that is evaluating efficacy and safety of TH-302 in patients with advanced solid tumors. Approximately 50 patients with metastatic and/or advanced unresectable soft tissue sarcoma are planned to enroll in the clinical trial at various sites in the United States. The dose escalation phase of the trial enrolled 17 patients. The primary objective of the dose escalation component of the study is to establish the maximum tolerated dose (MTD) and dose limiting toxicities of TH-302 in combination with doxorubicin. The MTD is 300mg/m2. Patients for whom no effective therapy is available or for whom monotherapy with doxorubicin is considered standard therapy are eligible for the trial. Patients who successfully complete one treatment cycle without evidence of significant treatment-related toxicity or progressive disease may continue to receive treatment for up to six cycles.
The Phase 2 portion of the trial will enroll an additional 30 patients at the MTD. The primary objective of the dose expansion component of the study is to make a preliminary assessment of the efficacy of TH-302 in combination with doxorubicin as measured by the progression-free rate at 6 months in patients previously untreated with chemotherapy.
The secondary endpoints of the trial include response, duration of response, progression-free rate at 3 months, progression-free survival, overall survival and various safety parameters. Tumor response will be evaluated at baseline and every six weeks using the Response Evaluation Criteria In Solid Tumors (RECIST).
For further information on the TH-CR-403 study, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8281 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.
402 Trial – Various Solid Tumors (Pancreatic, NSCLC, CRPC)
This is a Phase 1/2 dose escalation trial that is evaluating the efficacy and safety of TH-302 in patients with advanced solid tumors in combination with several approved chemotherapeutic agents. Approximately 90 patients with advanced solid tumors enrolled in the Phase 1, dose escalation portion of the clinical trial. The initial dose of TH-302 was 240mg/m2 which was the highest dose with no study drug-related grade 2 or greater toxicity in Phase 1 trial of TH-302. Up to six patients per dose level participated in the dose escalation phase of the trial. The maximum tolerated dose (MTD) has been established at 575mg/m2. The Phase 2 portion of the trial is enrolling an additional 72 patients at the MTD within each treatment arm as follows: gemcitabine in advanced pancreatic cancer patients, docetaxel in patients with castrate-resistant prostate cancer (CRPC) and non-small cell lung cancer (NSCLC) and pemetrexed in patients with non-squamous NSCLC.
TH-302 is being administered as a 30-minute intravenous infusion weekly for three weeks followed by one week off therapy in the gemcitabine arm, and weekly for two weeks followed by one week off therapy in the docetaxel and pemetrexed arms. Patients for whom no effective therapy is available or for whom monotherapy with one of the chemotherapy regimens is considered standard therapy, are eligible for the trial. Patients who successfully complete one treatment cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive treatment for up to six cycles (eight cycles for prostate cancer).
The primary objectives of the study are to determine the MTD and dose-limiting toxicities of TH-302 when used in combination with gemcitabine or docetaxel or pemetrexed in patients with advanced solid tumors and to assess the safety of TH-302 in these combination regimens. The primary objective of the dose expansion phase of the trial is to make a preliminary assessment of the efficacy of TH-302 based on tumor response rate and progression-free survival. Secondary objectives include establishing the pharmacokinetics and making a preliminary assessment of efficacy based on serum tumor markers of TH-302 when used in combination with gemcitabine, docetaxel or pemetrexed.
For further information on the TH-CR-402 study, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8281 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.
401 Trial – Various Solid Tumors
This is a randomized Phase 1 dose escalation trial that will evaluate efficacy and safety of TH-302 as monotherapy in patients with advanced solid tumors. Approximately 126 patients with advanced solid tumors are planned to enroll in the trial that is being conducted in the United States. Thirty-seven patients participated in the dose escalation phase of the trial. The maximum tolerated dose (MTD) was established at 575mg/m2. Thirty-six additional patients will be enrolled at the MTD with at least 6 patients in each of the following indications: metastatic melanoma, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In addition, a total of 18 additional patients with metastatic melanoma or SCLC and 12 patients with either transitional cell carcinoma (bladder, ureter or renal pelvis), squamous cell carcinoma (lung, anus, cervix, head and neck or skin) or hepatocellular carcinoma will be enrolled at a dose less than the MTD to help determine the recommended Phase 2 dose.
TH-302 is administered as a 30-minute intravenous infusion weekly for three weeks followed by one week off therapy. Patients who have received one or more regimens of chemotherapy, or for whom no effective therapy is available, are eligible for the trial. Patients will not receive any additional chemotherapy while receiving TH-302. Patients who successfully complete a four week treatment cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive treatment for up to six cycles. Tumor response will be measured at the end of cycles 2, 4 and 6.
For further information on the TH-CR-401 study, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8281 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.
