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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: ridaforolimus

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy & Research Center at UTHSCSA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Monica Mita, MD, The University of Texas Health Science Center at San Antonio

Publications and helpful links

Helpful Links

• Cancer Therapy & Research Center's Website

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 14, 2011
• First Posted (Estimate): February 15, 2011

Study Record Updates

• Last Update Posted (Estimate): July 12, 2012
• Last Update Submitted That Met QC Criteria: July 11, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: soft tissue sarcoma; sarcoma; Ridaforolimus; unresectable sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: IDD 10-09