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

26. august 2015 oppdatert av: 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.

Studieoversikt

Status

Fullført

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

46

Fase

  • Fase 1

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009
Eksperimentell: 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 navn:
  • AP23573
  • MK-8669
  • ridaforolimus var også kjent som deforolimus frem til mai 2009

Hva måler studien?

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Samarbeidspartnere

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. april 2003

Primær fullføring (Faktiske)

1. oktober 2005

Studiet fullført (Faktiske)

1. oktober 2005

Datoer for studieregistrering

Først innsendt

8. mai 2003

Først innsendt som oppfylte QC-kriteriene

9. mai 2003

Først lagt ut (Anslag)

12. mai 2003

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

27. august 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

26. august 2015

Sist bekreftet

1. august 2015

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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