Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)
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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 |
- 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 ]
- 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:
|
| 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:
|
| 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:
|
| 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:
|
| 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:
|
| 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:
|
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 |
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 More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT00060632 History of Changes |
| Other Study ID Numbers: | MK-8669-001, AP23573-02-101 |
| Study First Received: | May 8, 2003 |
| Last Updated: | May 23, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Merck:
|
Advanced, refractory or recurrent solid tumors |
Additional relevant MeSH terms:
|
Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders |
Hematologic Diseases Hemorrhagic Disorders Sirolimus Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on June 18, 2013