Effects of STM 434 Alone or in Combination With Liposomal Doxorubicin in Patients With Ovarian Cancer or Other Advanced Solid Tumors

NCT ID: NCT02262455

Last Updated: 2017-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2017-01-13

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Endometrial Cancer; Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

STM 434

Group Type: EXPERIMENTAL

STM 434

Intervention Type: DRUG

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.

STM 434 and Liposomal Doxorubicin

Group Type: EXPERIMENTAL

STM 434

Intervention Type: DRUG

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

Intervention Type: DRUG

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).

Interventions

STM 434

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.

Intervention Type: DRUG

Liposomal doxorubicin

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).

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Santa Maria Biotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Willis Navarro, MD

Role: STUDY_DIRECTOR

Santa Maria Biotherapeutics

Locations

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

Countries

United States

References

Bian X, Snow ZK, Zinn CJ, Gowan CC, Conley SM, Bratulin AL, Elhusseiny KM, Miller J, Tchkonia T, Kirkland JL, Lerman LO, Hickson LJ. Activin A Antagonism with Follistatin Reduces Kidney Fibrosis, Injury, and Cellular Senescence-Associated Inflammation in Murine Diabetic Kidney Disease. Kidney360. 2025 Mar 28;6(8):1278-1291. doi: 10.34067/KID.0000000776.

Reference Type: DERIVED

PMID: 40152935 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31068369 (View on PubMed)

Other Identifiers

STM-434-001

Identifier Type: -

Identifier Source: org_study_id