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

Sponsor

Santa Maria Biotherapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02262455

Collaborator

(none)

Enrollment

Locations

Arms

27.4

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Fallopian Tube Cancer Endometrial Cancer Solid Tumors	Drug: STM 434 Drug: Liposomal doxorubicin	Phase 1

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

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 Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Jan 13, 2017

Actual Study Completion Date :

Jan 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: STM 434	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.
Experimental: STM 434 and Liposomal Doxorubicin	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. 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).

Arm

Intervention/Treatment

Experimental: STM 434

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.

Experimental: STM 434 and Liposomal Doxorubicin

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.

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).

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [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.]
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.

Secondary Outcome Measures

Recommended Phase 2 dose (RP2D) [RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.]
To define the recommended Phase 2 dose (RP2D) in the event that there is no maximum tolerated dose (MTD) reached.
Radiographic response rate [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.]
To collect preliminary radiographic response data, including CT, MRI scans, during therapy with STM 434.
Muscle function and body composition [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.]
To collect preliminary anti-cachexia data, including body composition and laboratory parameters, during therapy with STM 434.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02114
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
4	South Texas Accelerated Research Therapeutics	San Antonio	Texas	United States	78229