SARC018: A Study of Mocetinostat and Gemcitabine in Patients With Metastatic Leiomyosarcoma

Study Overview
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Brief Summary
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This is an open-label, multi-center, Phase II trial studying the combination of mocetinostat and gemcitabine in patients who have previously demonstrated disease progression either while, or within six months after, receiving chemotherapy with a gemcitabine-based regimen.

Official Title
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A Phase II Study of Mocetinostat Administered With Gemcitabine for Patients With Metastatic Leiomyosarcoma With Progression or Relapse Following Prior Treatment With Gemcitabine-Containing Therapy

Conditions
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Metastatic Leiomyosarcoma

Intervention / Treatment
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* Drug: Mocetinostat
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Histologically documented leiomyosarcoma Prior systemic therapy with a gemcitabine containing regimen ECOG Performance Status of ≤ 1 Measurable metastatic disease with a target lesion that has increased in size by 20% in maximal dimension either during or within six months after treatment with chemotherapy using a gemcitabine containing regimen Adequate organ function within 14 days of study entry Patients or their legal representative must be able to read (or have read to them), understand, and sign a written informed consent (approved by the institutional review board) within 14 days prior to start of treatment. Exclusion Criteria: Concurrent, clinically significant, active malignancies (excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN] in situ or melanoma in situ) (Stage II portion only) Patients with baseline QTcF ≥ 480 msec Patients with uncontrolled concurrent illness, active infection requiring i.v. antibiotics, or uncontrolled infections, or a fever > 38.5°C on the day of scheduled dosing Patients with serious illnesses, medical conditions, or other medical history, including a prior history of pericarditis/pericardial effusion, or abnormal laboratory results, which, in the investigator's opinion, would be likely to interfere with a patient's participation in the study, or with the interpretation of the results Patients who have received any investigational drug within 28 days prior to Day 1 of study entry (an investigational drug is one for which there is no approved indication), or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 72 hours prior to starting study drug or a urine pregnancy test shall be done on Day 1 of Cycle 1 Women of child bearing potential and their partners must use an acceptable method of contraception while enrolled on this study, and for a period of 3 months following study drug treatment. Patients unwilling or unable to follow this guideline will be excluded. Investigators should follow their Institutional standard regarding acceptable methods of contraception. Known hypersensitivity to HDAC inhibitors or to any of the components of mocetinostat Known hypersensitivity to gemcitabine Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take mocetinostat with water and recommendation to avoid agents that increase gastric pH Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient's ability to sign the informed consent and undergo study procedures.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mocetinostat and gemcitabine<br>For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. | Drug: Mocetinostat<br>* Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2.<br>Drug: Gemcitabine<br>* Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Per RECIST 1.1) | Response rate (CR or PR) will be calculated by the number of patients achieving a response divided by the number of patients having been evaluated for response. Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameters of all target lesions. | 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | The duration of objective response will be measured from the time measurement criteria are first met until disease progression is objectively documented. | 27 months | 
| Progression Free Survival (PFS) | Progression free survival is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression Free Survival (PFS) is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression will be assessed by RECIST v. 1.1. | 27 months |