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

This study has been withdrawn prior to enrollment.
(Principal Investigator left institution.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01296659
First received: February 3, 2011
Last updated: July 11, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Soft Tissue Sarcoma
Drug: ridaforolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ib Study of Oral Ridaforolimus in Combination With Standard Chemotherapy for Patients With Advanced Unresectable Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Define maximum tolerated dose (MTD) [ Time Frame: 12-18 months ] [ Designated as safety issue: Yes ]
    Defining the maximum tolerated dose (MTD) and recommended Phase II dose for the combination ridaforolimus and SOC chemotherapy


Secondary Outcome Measures:
  • Number of Grade 2 or higher side effects with the combined therapy. [ Time Frame: 12-18 months ] [ Designated as safety issue: No ]
    Any evidence of antitumor activity--as measured by response rate (RECIST).

  • Pharmacokinetics [ Time Frame: 12-18 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 0
Study Start Date: February 2011
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: deforolimus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296659

Locations
United States, Texas
Cancer Therapy & Research Center at UTHSCSA
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Monica Mita, MD The University of Texas Health Science Center at San Antonio
  More Information

Additional Information:
No publications provided

Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01296659     History of Changes
Other Study ID Numbers: IDD 10-09
Study First Received: February 3, 2011
Last Updated: July 11, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
sarcoma
Ridaforolimus
soft tissue sarcoma
unresectable sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014