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A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Weekly Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies

Phase 1
18 Years
Not Enrolling
Tumors, Lymphoma, Multiple Myeloma

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Trial Information

A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Weekly Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies

The primary objectives of the study are to determine the safety, tolerability, and MTD of
ridaforolimus when administered once weekly for 4 weeks (4 week cycle). The secondary
objectives of the study are to characterize the pharmacokinetic profile of ridaforolimus, to
evaluate potential pharmacodynamic markers of ridaforolimus, and to obtain preliminary
information on the antineoplastic activity of ridaforolimus.

Protocol Outline: This is a dose-escalation study. Patients receive ridaforolimus over 30
minutes by intravenous infusion once weekly for 8 weeks (two 4-week cycles). 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.

Inclusion Criteria:

(Patients must meet each of the following criteria to be eligible for participation in the

- 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

- Patients with disease that is currently not amenable to surgical intervention.

- Patients with Karnofsky performance status of ≥ 70% (Eastern Cooperative Oncology
Group [ECOG] performance status of 0 or 1) and an anticipated life expectancy of ≥ 3

- 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

- Women who are pregnant or lactating.

- Patients with primary central nervous system (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

- 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 human immunodeficiency virus (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

- 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 replacement hormonal therapy for life-threatening non-oncology diseases.

- Herbal preparations or related over-the-counter (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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Time Frame:

Cycle 1 (within the first 4 weeks)

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2003

Completion Date:

October 2005

Related Keywords:

  • Tumors
  • Lymphoma
  • Multiple Myeloma
  • Advanced, refractory or recurrent solid tumors
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell