Study of Oral Ridaforolimus in Combination With Standard Chemotherapy for Soft Tissue Sarcoma

Study Overview
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Brief Summary
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Ridaforolimus has been tested in almost 2 dozen studies; however, it has not previously been tested in combination with the standard of care chemotherapy for sarcoma as this study will. We will be looking to see if Ridaforolimus given with SOC chemo (AIM or TG) is well tolerated and to determine a Phase 2 dose.

Official Title
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Phase Ib Study of Oral Ridaforolimus in Combination With Standard Chemotherapy for Patients With Advanced Unresectable Soft Tissue Sarcoma

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: ridaforolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or metastatic soft tissue sarcoma with histological or cytological proven disease. No more than 2 lines of chemotherapy in the metastatic setting in the dose escalation phase, and no more than one line of prior therapy in the expansion phase. ECOG performance status of ≤ 1 A minimum life expectancy > 3 months At least 4 weeks must have elapsed between prior investigational therapy, chemotherapy or radiotherapy and the first dose of ridaforolimus Adequate hematological, hepatic and renal function (hemoglobin ≥ 9g/dl, absolute neutrophil count [ANC] ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; bilirubin ≤ ULN; alkaline phosphatase ≤ 2.5 x ULN; AST, ALT ≤ 2.5 x ULN; albumin ≥ 2.5mg/dL; creatinine ≤ 1.5 x ULN) Serum cholesterol ≤ 350 mg/dL and triglycerides ≤400 mg/dL Signed informed consent Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of therapy and must use an approved contraceptive method as appropriate from the time of screening until 30 days after the last dose of study drug. Exclusion Criteria: Uncontrolled brain metastases, spinal cord compression, or carcinomatous meningitis. Clinically significant unexplained bleeding within 28 days prior to entering the trial Uncontrolled systemic vascular hypertension Clinically significant cardiovascular disease Newly diagnosed (within 3 months of enrollment) or poorly controlled type 1 or 2 diabetes Have received >350 mg/m2 total dose of Doxorubicin Active infection requiring prescribed intervention Other concurrent illness Major surgery within 28 days before trial entry, or incompletely healed surgical incision; minor surgery or procedures within 7 days Previous anthracycline lifetime exposure more than 350 mg/m2 would exclude patient form AIM Arm enrollment Pregnant or breastfeeding Known allergy to macrolide antibiotics Concurrent treatment with medications that induce or inhibit cytochrome P450 (CYP3A). Known history of HIV sero-positivity

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIM Arm<br>Ridaforolimus combined with doxorubicin/ifosfamide/mesma (AIM) | Drug: ridaforolimus<br>* Ridaforolimus administered orally 5 days per week in combination with standard chemotherapy<br>* Other names: deforolimus;|
| Experimental: TG Arm<br>Ridaforolimus combined with docetaxel and gemcitabine (TG) | Drug: ridaforolimus<br>* Ridaforolimus administered orally 5 days per week in combination with standard chemotherapy<br>* Other names: deforolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define maximum tolerated dose (MTD) | Defining the maximum tolerated dose (MTD) and recommended Phase II dose for the combination ridaforolimus and SOC chemotherapy | 12-18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Grade 2 or higher side effects with the combined therapy. | Any evidence of antitumor activity--as measured by response rate (RECIST). | 12-18 months | 
| Pharmacokinetics | Ridaforolimus pharmacokinetics when given in combination with SOC chemotherapy. Limited PK for SOC chemotherapy when combined with ridaforlimus. We will measure change in concentration of Ridaforolimus when combined with chemotherapy. | 12-18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sarcoma, Ridaforolimus, soft tissue sarcoma, unresectable sarcoma