- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00060632
Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)
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
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Cohort 1: Ridaforolimus 6.25 mg
|
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.
Andere Namen:
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Experimental: Cohort 2: Ridaforolimus 12.5 mg
|
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.
Andere Namen:
|
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Experimental: Cohort 3: Ridaforolimus 25 mg
|
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.
Andere Namen:
|
|
Experimental: Cohort 4: Ridaforolimus 50 mg
|
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.
Andere Namen:
|
|
Experimental: Cohort 5: Ridaforolimus 100 mg
|
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.
Andere Namen:
|
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Experimental: Cohort 6: Ridaforolimus 75 mg
|
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.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Maximum Tolerated Dose (MTD)
Zeitfenster: Cycle 1 (within the first 4 weeks)
|
Cycle 1 (within the first 4 weeks)
|
|
Number of Participants Reporting Adverse Events (AE)
Zeitfenster: Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
|
Number of Participants Discontinuing Due to AEs
Zeitfenster: Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Best Overall Tumor Response
Zeitfenster: 8 weeks
|
8 weeks
|
|
Maximum Concentration (Cmax) of Ridaforolimus
Zeitfenster: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
|
Area Under the Curve (AUC[0 to Infinity]) of Ridaforolimus
Zeitfenster: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
|
Apparent Terminal Half-Life (t1/2) of Ridaforolimus
Zeitfenster: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
|
Clearance (CL) of Ridaforolimus
Zeitfenster: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
|
Volume of Distribution at Steady State (Vss) of Ridaforolimus
Zeitfenster: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
|
Phosphorylated 4E Binding Protein 1 (Phospho-4E-BP1) Blood Levels
Zeitfenster: Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Herz-Kreislauf-Erkrankungen
- Gefäßerkrankungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Immunproliferative Erkrankungen
- Hämatologische Erkrankungen
- Hämorrhagische Störungen
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Neubildungen, Plasmazelle
- Multiples Myelom
- Physiologische Wirkungen von Arzneimitteln
- Antiinfektiva
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Antibakterielle Mittel
- Antibiotika, antineoplastische
- Antimykotika
- Sirolimus
Andere Studien-ID-Nummern
- 8669-001
- AP23573-02-101
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