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

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00060632
First received: May 8, 2003
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Tumors
Lymphoma
Multiple Myeloma
Drug: ridaforolimus
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1 (within the first 4 weeks) ] [ Designated as safety issue: Yes ]
  • Number of Participants Reporting Adverse Events (AE) [ Time Frame: Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months) ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Due to AEs [ Time Frame: Throughout study duration (Cycle 1 Day 1 to approximately 9 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Best Overall Tumor Response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Maximum Concentration (Cmax) of Ridaforolimus [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Area Under the Curve (AUC[0 to Infinity]) of Ridaforolimus [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Apparent Terminal Half-Life (t1/2) of Ridaforolimus [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Clearance (CL) of Ridaforolimus [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Volume of Distribution at Steady State (Vss) of Ridaforolimus [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Phosphorylated 4E Binding Protein 1 (Phospho-4E-BP1) Blood Levels [ Time Frame: Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1 ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: April 2003
Study Completion Date: October 2005
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Ridaforolimus 6.25 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Experimental: Cohort 2: Ridaforolimus 12.5 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Experimental: Cohort 3: Ridaforolimus 25 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Experimental: Cohort 4: Ridaforolimus 50 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Experimental: Cohort 5: Ridaforolimus 100 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009
Experimental: Cohort 6: Ridaforolimus 75 mg 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.

Other Names:
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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% (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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00060632     History of Changes
Other Study ID Numbers: 8669-001, AP23573-02-101
Study First Received: May 8, 2003
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Advanced, refractory or recurrent solid tumors

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014