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

26 augustus 2015 bijgewerkt door: Merck Sharp & Dohme LLC

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

Studie Overzicht

Toestand

Voltooid

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

46

Fase

  • Fase 1

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus
Experimenteel: 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:
  • AP23573
  • MK-8669
  • ridaforolimus was tot mei 2009 ook bekend als deforolimus

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Maximum Tolerated Dose (MTD)
Tijdsspanne: Cycle 1 (within the first 4 weeks)
Cycle 1 (within the first 4 weeks)
Number of Participants Reporting Adverse Events (AE)
Tijdsspanne: 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
Tijdsspanne: Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
Throughout study duration (Cycle 1 Day 1 to approximately 9 months)

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Best Overall Tumor Response
Tijdsspanne: 8 weeks
8 weeks
Maximum Concentration (Cmax) of Ridaforolimus
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 april 2003

Primaire voltooiing (Werkelijk)

1 oktober 2005

Studie voltooiing (Werkelijk)

1 oktober 2005

Studieregistratiedata

Eerst ingediend

8 mei 2003

Eerst ingediend dat voldeed aan de QC-criteria

9 mei 2003

Eerst geplaatst (Schatting)

12 mei 2003

Updates van studierecords

Laatste update geplaatst (Schatting)

27 augustus 2015

Laatste update ingediend die voldeed aan QC-criteria

26 augustus 2015

Laatst geverifieerd

1 augustus 2015

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op ridaforolimus

3
Abonneren