Study of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00093080
First received: September 30, 2004
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to assess the efficacy of ridaforolimus when administered once daily for 5 consecutive days (QDx5) every two weeks in participants with advanced sarcoma.


Condition Intervention Phase
Leiomyosarcoma
Liposarcoma
Osteosarcoma
Sarcoma, Soft Tissue
Metastases
Drug: ridaforolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AP23573, An mTOR Inhibitor, in Patients With Advanced Sarcoma

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants with Clinical Benefit Response (CBR) Using Response Criteria in Solid Tumors (RECIST) [ Time Frame: Day 1 up to 4 years or discontinuation from study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to Tumor Progression [ Time Frame: Day 1 up to the first observation of disease progression, death, or the date of the last evaluation of response (up to 4 years) ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: Day 1 to the first observation of disease progression, death, or the date of the last evaluation of response (up to 4 years) ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Day 1 to the date of death, or the date of last contact (up to 4 years) ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Day 1 up to the first observation of disease progression, death, or the date of the last evaluation of response (up to 4 years) ] [ Designated as safety issue: No ]
  • Number of participants experiencing adverse events [ Time Frame: From first dose up to 30 days after last dose (up to 1 year) ] [ Designated as safety issue: Yes ]
  • Number of participants who discontinued study drug due to adverse events [ Time Frame: From first dose up to the last dose (up to 1 year) ] [ Designated as safety issue: Yes ]
  • Mean ridaforolimus blood levels within 5 minutes post intravenous infusion [ Time Frame: Day 1 and Day 5 of Cycle 1 ] [ Designated as safety issue: No ]

Enrollment: 216
Study Start Date: October 2004
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ridaforolimus
12.5 mg of ridaforolimus is given intravenously over 30 minutes once daily for 5 days, every 2 weeks
Drug: ridaforolimus
12.5 mg of ridaforolimus is given intravenously over 30 minutes once daily for 5 days, every 2 weeks
Other Names:
  • deforolimus (until May 2009)
  • AP23573
  • MK-8669

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥15 years of age with metastatic and/or unresectable sarcomas of the following histological subgroups: Bone sarcomas, such as osteosarcoma and Ewings sarcoma; Leiomyosarcoma; Liposarcomas; Any other soft tissue sarcoma except gastrointestinal stromal tumors (GIST). Patients with well-differentiated liposarcoma or desmoid tumors must have demonstrated progressive disease within the previous 6 months
  • Presence of at least one measurable lesion that: Can be accurately measured in at least one dimension with longest diameter ≥20 mm using conventional techniques or ≥10 mm with spiral computerized tomography (CT) scan (or otherwise at least twice the reconstruction interval for CT or magnetic resonance imaging [MRI] scans)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Minimum life expectancy of 3 months
  • Adequate renal and hepatic function, as specified in the protocol
  • Adequate bone marrow function, as specified in the protocol
  • Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL
  • Male and female patients who are not surgically sterile or postmenopausal must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug
  • Able to understand and give written informed consent

Exclusion Criteria:

  • Women who are pregnant or lactating
  • Presence of brain metastases
  • Prior therapy with rapamycin, rapamycin analogues or tacrolimus
  • Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of ridaforolimus
  • Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by National Cancer Institute (NCI) toxicity criteria)
  • Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)
  • Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug
  • Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
  • Significant uncontrolled cardiovascular disease
  • Active infection requiring systemic therapy
  • Known human immunodeficiency virus (HIV) infection
  • Treatment with any investigational agent within 4 weeks prior to the first dose of ridaforolimus
  • Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for 2 weeks prior to first planned dose of study drug
  • Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of ridaforolimus
  • Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluating the safety of the study drug
  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.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00093080     History of Changes
Other Study ID Numbers: 8669-018, AP23573-04-202, 2004-002231-92
Study First Received: September 30, 2004
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Metastatic and/or unresectable soft tissue or

Additional relevant MeSH terms:
Leiomyosarcoma
Liposarcoma
Neoplasm Metastasis
Osteosarcoma
Sarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Adipose Tissue
Neoplastic Processes
Pathologic Processes
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
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 July 31, 2014