- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00288431
Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin (8669-015)
July 21, 2015 updated by: Merck Sharp & Dohme LLC
A Phase 1B, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin
This study is designed to determine the safety, tolerability and maximum tolerated dose of Oral AP23573 in combination with Doxorubicin
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
37
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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:
administered at 60 mg/m2 intravenously every 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
determine the maximum tolerated dose (MTD) of oral AP23573 in combination with doxorubicin
Time Frame: Duration of study
|
Duration of study
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Describe the antitumor activity of the study drug combination for each dosing schedule
Time Frame: Duration of study
|
Duration of study
|
examine the pharmacokinetics of oral AP23573 and doxorubicin when given in combination
Time Frame: Duration of study
|
Duration of study
|
Examine pharmacodynamic characteristics of AP23573 for those patients enrolled into the expanded MTD cohorts only
Time Frame: Duration of study
|
Duration of study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2006
Primary Completion (Actual)
July 1, 2008
Study Completion (Actual)
July 1, 2008
Study Registration Dates
First Submitted
February 6, 2006
First Submitted That Met QC Criteria
February 6, 2006
First Posted (Estimate)
February 8, 2006
Study Record Updates
Last Update Posted (Estimate)
July 22, 2015
Last Update Submitted That Met QC Criteria
July 21, 2015
Last Verified
July 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Doxorubicin
- Sirolimus
Other Study ID Numbers
- 8669-015
- AP23573-05-107
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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