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Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin
This study is ongoing, but not recruiting participants.
Sponsored by: Ariad Pharmaceuticals
Information provided by: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00288431
  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: AP23573
Drug: Doxorubicin
Phase I

MedlinePlus related topics: Cancer Soft Tissue Sarcoma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride AP 23573
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
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

Further study details as provided by Ariad Pharmaceuticals:

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
Estimated Study Completion Date: December 2008
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AP23573
    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: 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
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
Ariad Pharmaceuticals
Investigators
Study Director: Frank Haluska, M.D. Ariad Pharmaceuticals
  More Information

Responsible Party: ARIAD Pharmaceuticals, Inc. ( Frank Haluska, M.D. )
Study ID Numbers: AP23573-05-107
Study First Received: February 6, 2006
Last Updated: June 30, 2008
ClinicalTrials.gov Identifier: NCT00288431  
Health Authority: United States: Food and Drug Administration

Keywords provided by Ariad Pharmaceuticals:
cancer
sarcoma

Study placed in the following topic categories:
Neoplasms, Connective and Soft Tissue
Malignant mesenchymal tumor
Sarcoma
Doxorubicin
Soft tissue sarcomas

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009