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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02262455
• Other study ID #: STM-434-001
• Status: Completed
• Phase: Phase 1
• First received: September 29, 2014
• Last updated: February 10, 2017
• Start date: October 2014
• Est. completion date: January 13, 2017

Study information

• Verified date: February 2017
• Source: Santa Maria Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 13, 2017
• Est. primary completion date: January 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Solid Tumors

Intervention

Drug:
• 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.
• 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).

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Santa Maria Biotherapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.
Secondary	Radiographic response rate	To collect preliminary radiographic response data, including CT, MRI scans, during therapy with STM 434.	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.
Secondary	Muscle function and body composition	To collect preliminary anti-cachexia data, including body composition and laboratory parameters, during therapy with STM 434.	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.