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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Endometrial Cancer, Solid Tumors

Intervention / Treatment
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* Drug: STM 434
* Drug: Liposomal doxorubicin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STM 434<br> | Drug: STM 434<br>* 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.<br>|
| Experimental: STM 434 and Liposomal Doxorubicin<br> | Drug: STM 434<br>* 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.<br>Drug: Liposomal doxorubicin<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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