Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin (8669-015)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00288431
First received: February 6, 2006
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

This study is designed to determine the safety, tolerability and maximum tolerated dose of Oral AP23573 in combination with Doxorubicin


Condition Intervention Phase
Cancer
Sarcoma
Drug: ridaforolimus
Drug: Doxorubicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1B, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin

Resource links provided by NLM:


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

Primary Outcome Measures:
  • determine the maximum tolerated dose (MTD) of oral AP23573 in combination with doxorubicin [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Describe the antitumor activity of the study drug combination for each dosing schedule [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  • examine the pharmacokinetics of oral AP23573 and doxorubicin when given in combination [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  • Examine pharmacodynamic characteristics of AP23573 for those patients enrolled into the expanded MTD cohorts only [ Time Frame: Duration of study ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: February 2006
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Different schedules and routes of administration of AP23573 will be examined. For each schedule, AP23573 + Doxorubicin will be co-administered on Day 1 of a 3-week cycle. AP23573 will be given orally and will range in dose from 10-30 mg per dose.
Drug: ridaforolimus
Different schedules and routes of administration of AP23573 will be examined. For each schedule, AP23573 + Doxorubicin will be co-administered on Day 1 of a 3-week cycle. AP23573 will be given orally and will range in dose from 10-30 mg per dose.
Other Names:
  • deforolimus
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Drug: Doxorubicin
administered at 60 mg/m2 intravenously every 3 weeks

Detailed Description:

The primary objective is to determine the maximum tolerated dose (MTD) of AP23573 in combination with doxorubicin, to characterize the safety profile of AP23573 in combination with doxorubicin, and to examine the pharmacokinetics of AP23573 and doxorubicin when given in combination to patients with advanced malignancies.

  Eligibility

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

Inclusion Criteria:

  • Age ≥ 18 years with a histological/cytological diagnosis of advanced tumor, preferentially breast, sarcoma, ovarian, endometrial or other tumor types for which treatment with anthracycline therapy is indicated
  • Prior cumulative doxorubicin exposure less than 400 mg/m2
  • An ECOG performance status of 0 or 1
  • Adequate cardiovascular function
  • Measurable disease according to modified RECIST criteria
  • Adequate hematological, renal and hepatic functions
  • Able to understand and give voluntary written informed consent

Exclusion Criteria:

  • Women who are pregnant or lactating
  • Presence of active brain metastases. Patients with treated brain metastases will be eligible if they are on a stable dose of corticosteroids or are without change in brain disease status for at least 4 weeks following related therapy (e.g., whole brain radiation, surgery)
  • Prior treatment with CCI-779, rapamycin, or any other mTOR inhibitor
  • Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of AP23573; the interval is ≥ 2 weeks for signal transduction inhibitors with a half-life known to be <24 hours, and is ≥ 6 weeks for nitrosourea or mitomycin. Exception: Concurrent treatment with LHRH agonists is allowed for patients with prostate cancer.
  • Ongoing toxicity associated with prior anticancer therapy other than alopecia and ≤ Grade 1 peripheral neuropathy by 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 any excipient contained in the study drug
  • Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
  • Significant uncontrolled cardiovascular disease
  • Any active infection requiring prescribed intervention
  • Any other concurrent illness which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug
  • Any pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption
  • Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug
  • Concurrent treatment with medications that induce or inhibit cytochrome P450 (CYP3A)
  • Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of AP23573
  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: NCT00288431

Locations
United States, California
Sant P. Chawla, M.D. Inc.
Santa Monica, California, United States, 90403
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Ariad Pharmaceuticals
Investigators
Study Director: Frank Haluska, M.D. Ariad Pharmaceuticals
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00288431     History of Changes
Other Study ID Numbers: 8669-015, AP23573-05-107
Study First Received: February 6, 2006
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
cancer
sarcoma

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

ClinicalTrials.gov processed this record on July 23, 2014