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

26. august 2015 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

46

Fase

  • Fase 1

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009
Eksperimentel: 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.

Andre navne:
  • AP23573
  • MK-8669
  • ridaforolimus var også kendt som deforolimus indtil maj 2009

Hvad måler undersøgelsen?

Primære resultatmål

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

Sekundære resultatmål

Resultatmål
Tidsramme
Best Overall Tumor Response
Tidsramme: 8 weeks
8 weeks
Maximum Concentration (Cmax) of Ridaforolimus
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. april 2003

Primær færdiggørelse (Faktiske)

1. oktober 2005

Studieafslutning (Faktiske)

1. oktober 2005

Datoer for studieregistrering

Først indsendt

8. maj 2003

Først indsendt, der opfyldte QC-kriterier

9. maj 2003

Først opslået (Skøn)

12. maj 2003

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

27. august 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

26. august 2015

Sidst verificeret

1. august 2015

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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