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

Overview[ - collapse ][ - ]

Purpose This study is designed to determine the safety, tolerability and maximum tolerated dose of Oral AP23573 in combination with Doxorubicin
ConditionCancer
Sarcoma
InterventionDrug: ridaforolimus
Drug: Doxorubicin
PhasePhase 1
SponsorMerck Sharp & Dohme Corp.
Responsible PartyMerck Sharp & Dohme Corp.
ClinicalTrials.gov IdentifierNCT00288431
First ReceivedFebruary 6, 2006
Last UpdatedAugust 22, 2013
Last verifiedAugust 2013

Tracking Information[ + expand ][ + ]

First Received DateFebruary 6, 2006
Last Updated DateAugust 22, 2013
Start DateFebruary 2006
Estimated Primary Completion DateJuly 2008
Current Primary Outcome Measuresdetermine the maximum tolerated dose (MTD) of oral AP23573 in combination with doxorubicin [Time Frame: Duration of study] [Designated as safety issue: Yes]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleSafety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin (8669-015)(COMPLETED)
Official TitleA Phase 1B, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin
Brief Summary
This study is designed to determine the safety, tolerability and maximum tolerated dose of
Oral AP23573 in combination with Doxorubicin
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.
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Cancer
  • Sarcoma
InterventionDrug: 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
Study Arm (s)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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment37
Estimated Completion DateJuly 2008
Estimated Primary Completion DateJuly 2008
Eligibility 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00288431
Other Study ID Numbers8669-015
Has Data Monitoring CommitteeNo
Information Provided ByMerck Sharp & Dohme Corp.
Study SponsorMerck Sharp & Dohme Corp.
CollaboratorsAriad Pharmaceuticals
Investigators Study Director: Frank Haluska, M.D. Ariad Pharmaceuticals
Verification DateAugust 2013

Locations[ + expand ][ + ]

Sant P. Chawla, M.D. Inc.
Santa Monica, California, United States, 90403
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106