Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00060632
• Other study ID #: 8669-001
• Secondary ID: AP23573-02-101
• Status: Completed
• Phase: Phase 1
• First received: May 8, 2003
• Last updated: August 26, 2015
• Start date: April 2003
• Est. completion date: October 2005

Study information

• Verified date: August 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase 1 trial to determine the safety, tolerability and maximum tolerated dose (MTD) of ridaforolimus in patients with refractory or recurrent malignancies, including myeloma and lymphoma.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 2005
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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% (Eastern Cooperative Oncology Group [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 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 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 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 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 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.

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Multiple Myeloma
• Tumors

Intervention

Drug:
• ridaforolimus
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Ariad Pharmaceuticals

References & Publications (1)

Hartford CM, Desai AA, Janisch L, Karrison T, Rivera VM, Berk L, Loewy JW, Kindler H, Stadler WM, Knowles HL, Bedrosian C, Ratain MJ. A phase I trial to determine the safety, tolerability, and maximum tolerated dose of deforolimus in patients with advanced malignancies. Clin Cancer Res. 2009 Feb 15;15(4):1428-34. doi: 10.1158/1078-0432.CCR-08-2076. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		Cycle 1 (within the first 4 weeks)	Yes
Primary	Number of Participants Reporting Adverse Events (AE)		Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)	Yes
Primary	Number of Participants Discontinuing Due to AEs		Throughout study duration (Cycle 1 Day 1 to approximately 9 months)	Yes
Secondary	Best Overall Tumor Response		8 weeks	No
Secondary	Maximum Concentration (Cmax) of Ridaforolimus		Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1	No
Secondary	Area Under the Curve (AUC[0 to Infinity]) of Ridaforolimus		Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1	No
Secondary	Apparent Terminal Half-Life (t1/2) of Ridaforolimus		Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1	No
Secondary	Clearance (CL) of Ridaforolimus		Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1	No
Secondary	Volume of Distribution at Steady State (Vss) of Ridaforolimus		Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1	No
Secondary	Phosphorylated 4E Binding Protein 1 (Phospho-4E-BP1) Blood Levels		Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1	No