Clinical trial NCT02262455: Effects of STM 434 Alone or in Combination With Liposomal Doxorubicin in Patients With Ovarian Cancer or Other Advanced Solid Tumors
Official title: An Open-Label Multiple Ascending Dose Phase 1/1B Pharmacokinetic and Pharmacodynamic Study of STM 434, an Activin Type 2B Receptor Fc Fusion, Alone and in Combination With Liposomal Doxorubicin in Patients With Ovarian Cancer or Other Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Endometrial Cancer
Solid Tumors
Keywords: Serous tumor
Granulosa tumor
Clear Cell tumor
Endometrial cancer
Advanced solid tumors
Adenocarcinoma
Prostate cancer
Head and Neck cancer
Lung cancer
Non-small cell lung cancer
Small cell lung cancer
Gastric cancer
Kidney cancer
Pancreatic cancer
Breast cancer
Colorectal cancer
Bladder cancer
Esophagus cancer
Liver cancer
Hepatobiliary cancer
Skin cancer
Lead sponsor: Santa Maria Biotherapeutics
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Males and postmenopausal females, 18 years or older
* Advanced solid tumors with histologic diagnosis confirming cancer
* Patients with recurrent metastatic or locally advanced disease considered refractory or intolerant to all standard treatment available for their tumor, or those tumors for which no standard treatment is available
* Subjects with serous ovarian/fallopian tube/primary peritoneal, granulosa cell tumors or clear cell tumors considered platinum refractory/resistant, defined as having at least one prior platinum-based chemotherapeutic regimen with a subsequent platinum-free interval of \< 12 months, having progression during platinum-based therapy, or having persistent disease after a platinum-based therapy, are eligible. Intolerant subjects, defined as unable to receive further platinum due to toxicity, are eligible.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Informed consent

Exclusion Criteria:

* History of gastrointestinal bleeding within the past 6 months
* History of epistaxis requiring medical/surgical intervention (such as nasal packing) within the past 6 months
* History of central nervous system hemorrhage
* History of bleeding diathesis or known qualitative platelet defect (including von Willebrand disease)
* Ongoing need for therapeutic anticoagulants (full dose heparin, warfarin, factor Xa or direct thrombin inhibitors; rivaroxaban, apixaban, dabigatran) chronic use of aspirin or anti-platelet agents (ticlopidine or clopidogrel)
* History of hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu syndrome)
* Myocardial infarction, unstable angina within the past 6 months, or congestive heart failure New York Heart Association Class II or greater
* Chemotherapy, hormonal therapy or radiation therapy within the past 3 weeks, antibody/biologic therapy within 5 half-lives or within the past 4 weeks (whichever is longer)
* Current bowel obstruction
* Brain metastasis
* Known HIV infection and/or active Hepatitis B or C infection
* Prior treatment with any investigational product within the past 4 weeks
* Not willing to use contraception (inclusive of abstinence)

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 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.
Secondary outcomes:
measure: Recommended Phase 2 dose (RP2D)
timeFrame: RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.
measure: Radiographic response rate
timeFrame: 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.
measure: Muscle function and body composition
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
affiliation: Santa Maria Biotherapeutics
name: Willis Navarro, MD
role: STUDY_DIRECTOR
References:
citation: Tao JJ, Cangemi NA, Makker V, Cadoo KA, Liu JF, Rasco DW, Navarro WH, Haqq CM, Hyman DM. First-in-Human Phase I Study of the Activin A Inhibitor, STM 434, in Patients with Granulosa Cell Ovarian Cancer and Other Advanced Solid Tumors. Clin Cancer Res. 2019 Sep 15;25(18):5458-5465. doi: 10.1158/1078-0432.CCR-19-1065. Epub 2019 May 8.