search
Back to results

Safety Study of AP23573 in Patients With Advanced, Refractory or Recurrent Malignancies (8669-013)(COMPLETED)

Primary Purpose

Tumors, Lymphoma, Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ridaforolimus
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tumors focused on measuring Advanced, refractory or recurrent solid tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: (Patients must meet each of the following criteria to be eligible for participation in the study). Male or female patients, ≥ 18 years of age. Patients with a documented measurable or evaluable malignancy, including myeloma or lymphoma, that is recurrent, advanced, or metastatic. Patients with disease that is currently refractory to, or not amenable to, standard therapy. Patients with disease that is currently not amenable to surgical intervention. Patients with Karnofsky performance status of ≥ 70% (ECOG performance status of 0 or 1) and an anticipated life expectancy of ≥ 3 months. Patients either not of childbearing potential, or agreeing to use a medically effective method of contraception. Patients with the ability to understand and give written informed consent. Exclusion Criteria: (Patients meeting any of the following criteria are ineligible for participation in the study) Women who are pregnant or lactating. Patients with primary CNS malignancies. Patients with leukemia, any form. Patients with certain hematologic abnormalities. Patients with certain serum chemistry abnormalities at baseline. Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween 80) or any other excipient contained in the test drug formulation. Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). Patients with significant cardiovascular disease. Patients with active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy. Note: 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). Patients with known HIV infection. Patients with any active infection. Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 2 weeks prior to study entry. Note: Patients having undergone recent placement of a central venous access port will be considered eligible for enrollment if they have recovered. Patients who have 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 evaluation of the safety of the test drug. Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies. Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements. Drugs and Other Treatments to be Excluded (Either during or within 4 weeks prior to study entry, unless otherwise noted) Chemotherapeutic agents (standard or experimental). Other antineoplastic agents. Immunotherapy (including vaccines) or biological response modifier therapy. Systemic hormonal therapy. Herbal preparations or related OTC preparations containing herbal ingredients (e.g., St John's Wort) during or within 2 weeks prior to study entry. Any prior therapy with rapamycin, CCI-779, or any other rapamycin analog. Any other experimental therapy during the course of the study. Radiotherapy for the primary malignancy or metastases.

Sites / Locations

  • Cancer Therapy and Research Center, University of Texas Health Center at San Antonio

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

There are sequential dosage cohorts ranging from 3 mg - 225 mg per dose. AP23573 is given intravenously over 30 minutes, administered once daily for 5 days every 2 weeks.

Outcomes

Primary Outcome Measures

To determine safety, tolerability, and maximum tolerated dose of AP23573 when administered once daily for 5 days on a every 2 week schedule

Secondary Outcome Measures

Full Information

First Posted
May 8, 2003
Last Updated
August 26, 2015
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT00060645
Brief Title
Safety Study of AP23573 in Patients With Advanced, Refractory or Recurrent Malignancies (8669-013)(COMPLETED)
Official Title
A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Daily x 5 Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
Phase 1 trial to determine the safety, tolerability and maximum tolerated dose (MTD) of AP23573 in patients with refractory or recurrent malignancies, including myeloma and lymphoma.
Detailed Description
The primary objectives of the study are to determine the safety, tolerability, and MTD of AP23573, when administered once daily for 5 days to be repeated every 2 weeks (two 2-week courses equals 1 cycle). The secondary objectives of the study are to characterize the pharmacokinetic profile of AP23573, to evaluate potential pharmacodynamic markers of AP23573, and to obtain preliminary information on the antineoplastic activity of AP23573. Protocol Outline: This is a dose-escalation study. Patients receive AP23573 over 30 minutes by intravenous infusion once daily for 5 days to be repeated every 2 weeks. If tolerated, a total of at least 2 cycles will be administered (8-week treatment period). Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tumors, Lymphoma, Multiple Myeloma
Keywords
Advanced, refractory or recurrent solid tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
There are sequential dosage cohorts ranging from 3 mg - 225 mg per dose. AP23573 is given intravenously over 30 minutes, administered once daily for 5 days every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
ridaforolimus
Other Intervention Name(s)
deforolimus, AP23573, MK-8669, ridaforolimus was also known as deforolimus until May 2009
Intervention Description
There are sequential dosage cohorts ranging from 3 mg - 225 mg per dose. AP23573 is given intravenously over 30 minutes, administered once daily for 5 days every 2 weeks.
Primary Outcome Measure Information:
Title
To determine safety, tolerability, and maximum tolerated dose of AP23573 when administered once daily for 5 days on a every 2 week schedule
Time Frame
Duration of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (Patients must meet each of the following criteria to be eligible for participation in the study). Male or female patients, ≥ 18 years of age. Patients with a documented measurable or evaluable malignancy, including myeloma or lymphoma, that is recurrent, advanced, or metastatic. Patients with disease that is currently refractory to, or not amenable to, standard therapy. Patients with disease that is currently not amenable to surgical intervention. Patients with Karnofsky performance status of ≥ 70% (ECOG performance status of 0 or 1) and an anticipated life expectancy of ≥ 3 months. Patients either not of childbearing potential, or agreeing to use a medically effective method of contraception. Patients with the ability to understand and give written informed consent. Exclusion Criteria: (Patients meeting any of the following criteria are ineligible for participation in the study) Women who are pregnant or lactating. Patients with primary CNS malignancies. Patients with leukemia, any form. Patients with certain hematologic abnormalities. Patients with certain serum chemistry abnormalities at baseline. Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween 80) or any other excipient contained in the test drug formulation. Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). Patients with significant cardiovascular disease. Patients with active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy. Note: 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). Patients with known HIV infection. Patients with any active infection. Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 2 weeks prior to study entry. Note: Patients having undergone recent placement of a central venous access port will be considered eligible for enrollment if they have recovered. Patients who have 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 evaluation of the safety of the test drug. Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies. Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements. Drugs and Other Treatments to be Excluded (Either during or within 4 weeks prior to study entry, unless otherwise noted) Chemotherapeutic agents (standard or experimental). Other antineoplastic agents. Immunotherapy (including vaccines) or biological response modifier therapy. Systemic hormonal therapy. Herbal preparations or related OTC preparations containing herbal ingredients (e.g., St John's Wort) during or within 2 weeks prior to study entry. Any prior therapy with rapamycin, CCI-779, or any other rapamycin analog. Any other experimental therapy during the course of the study. Radiotherapy for the primary malignancy or metastases.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Haluska, M.D., Ph.D.
Organizational Affiliation
Ariad Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Therapy and Research Center, University of Texas Health Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18202410
Citation
Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, Patnaik A, Mathews L, Ricart AD, Mays T, Knowles H, Rivera VM, Kreisberg J, Bedrosian CL, Tolcher AW. Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol. 2008 Jan 20;26(3):361-7. doi: 10.1200/JCO.2007.12.0345.
Results Reference
result

Learn more about this trial

Safety Study of AP23573 in Patients With Advanced, Refractory or Recurrent Malignancies (8669-013)(COMPLETED)

We'll reach out to this number within 24 hrs