This is a Phase I study to test the safety, pharmacokinetics and effectiveness of STM 434 alone, or in combination with liposomal doxorubicin, in patients with ovarian cancer or other advanced solid tumors.
This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body), and anti-tumor activities of STM 434 (an inhibitor of activin A) in patients with ovarian cancer and other advanced solid tumors. The study will be conducted in 3 phases (Part 1, Part 2 and Part 3). In the first part of the study (Part 1), which will enroll patients with multiple solid tumor types, the maximum tolerated dose (MTD) of STM 434 will be determined for use in the second and third parts of the study (Parts 2 and 3). In the second part (Part 2), which will enroll patients with ovarian cancer, STM 434 will be administered alone, and in the third part (Part 3), which will enroll patients with ovarian cancer, STM 434 will be given together with a chemotherapy called liposomal doxorubicin. Doses of STM 434 (starting at 0.25 mg/kg up to a maximum of 4 mg/kg) will be taken on one of three dosing schedules to determine the MTD. Patients will continue taking STM 434 until their tumor progresses. Serial blood samples will be collected for pharmacokinetic and pharmacodynamic testing and safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
STM 434 will be administered by IV injection. There are five planned dose levels, from 0.25mg/kg to 4mg/kg, which is dependent on the cohort (group) a participant is assigned to.
Liposomal doxorubicin (40 mg/m2) will be administered once every 28 days by IV infusion prior to STM 434 for those participants enrolled in Part 3 of the trial. Liposomal doxorubicin will be administered for a maximum of 6 cycles (each cycle being 28 days).
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Maximum Tolerated Dose (MTD)
To define the maximum tolerated dose (MTD) of STM 434 administered alone or in combination with liposomal doxorubicin chemotherapy in patients with ovarian cancer or other advanced solid tumors.
Time frame: MTD will be assessed for STM 434 alone in Part 1 and in combination with liposomal doxorubicin in Part 3 once the last subject in each cohort completes 28 days of treatment.
Recommended Phase 2 dose (RP2D)
To define the recommended Phase 2 dose (RP2D) in the event that there is no maximum tolerated dose (MTD) reached.
Time frame: RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.
Radiographic response rate
To collect preliminary radiographic response data, including CT, MRI scans, during therapy with STM 434.
Time frame: Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months, for up to 24 months.
Muscle function and body composition
To collect preliminary anti-cachexia data, including body composition and laboratory parameters, during therapy with STM 434.
Time frame: Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months for up to 24 months.
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