- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01688791
A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)
9. februar 2015 oppdatert av: Endocyte
A Phase I Dose Escalation Study Evaluating Vintafolide (MK-8109) Chemotherapy Alone or in Combination in Adult Subjects With Advanced Cancers
This trial will be conducted in three parts.
Part A is a dose escalation trial followed by a dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants.
The primary hypothesis of this trial is that administration of vintafolide in combination with carboplatin and paclitaxel is safe and tolerable.
Part B is a single dose, dose escalation, pharmacokinetic (PK), and QTc interval trial.
The primary objectives include determination of the maximum single tolerated dose of vintafolide and to evaluate the effect of this single maximum dose on the QTc interval.
Part C is a weekly dose escalation trial of vintafolide followed by a dose confirmation.
The primary hypothesis of this part is that weekly vintafolide has acceptable safety and tolerability in participants with advanced cancers.
Studieoversikt
Status
Avsluttet
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
37
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 for all participants:
- Histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist or is unacceptable to the participant
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- At least one measurable metastatic or recurrent lesion
- No history of a previous malignancy with the exception of cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or adequately treated localized prostate carcinoma; or has undergone potentially curative therapy with no evidence of disease for five years
- Adequate organ function
- Female participants of childbearing potential must be willing to use acceptable methods of birth control or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study therapy
- Male participants must agree to use an adequate method of contraception for heterosexual activity starting with the first dose of study therapy through 90 days after the last dose of study therapy
Inclusion criteria for Part A:
- Tumor lesions characterized as folate receptor (FR) 100% as determined by an etarfolide Sequential Single Photon Emission Computed Tomography (SPECT) and CT scan
- Histologically-confirmed diagnosis of locally advanced or metastatic or recurrent endometrial cancer
Inclusion criteria for Parts B & C:
- Must have an etarfolatide SPECT/CT scan to determine FR status
Exclusion criteria for all participants:
- Part A & Part C if enrolled after completion of Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
- Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 3 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
- Currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study
- Part A, dose escalation, Parts B and C: More than 3 prior cytotoxic regimens for metastatic disease.
- Part A, dose confirmation: Has received more than 2 prior cytotoxic regimens for metastatic disease.
- Primary central nervous system (CNS) tumor
- Active CNS metastases and/or carcinomatous meningitis.
- Known hypersensitivity to the components of the study therapy or its analogs
- Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis
- Bowel occlusion or sub-occlusion
- Prior whole abdominal or whole pelvis radiation therapy or radiation therapy to >10% of the bone marrow at any time in the past or prior radiation therapy within the last 3 years to the breast / sternum, head, or neck
- Requires anti-folate therapy for the management of co-morbid conditions
- Known regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
- Pregnant or breastfeeding or expecting to conceive, or donate sperm within the span of the study
- Human Immunodeficiency Virus (HIV)-positive
- Active Hepatitis B or C
- Symptomatic ascites or pleural effusion.
- History of stem cell or bone marrow transplant
Exclusion Criteria for Part B:
- Permanent pacemaker
- Unable to refrain from use of all concomitant medications on Day 1
- Structural heart disease, history of myocardial infarction (MI), or unstable angina
- History of cardiac arrhythmia, congestive heart failure (CHF), sick sinus syndrome, second or third degree atrioventricular (AV) block
- History of risk factors for Torsades de Pointes such as CHF, uncorrected hypokalemia, family history of long QT syndrome
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: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Part A: Vintafolide BIW
Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle.
Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle.
Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
|
Andre navn:
|
|
Eksperimentell: Part A: Vintafolide TIW
Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle.
Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle.
Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
|
Andre navn:
|
|
Eksperimentell: Parts B & C: Vintafolide Single Dose & Weekly (QW)
Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation.
Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.
|
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Parts A and C: Number of participants with dose-limiting toxicities (DLTs)
Tidsramme: Cycle 1 (21 days)
|
Cycle 1 (21 days)
|
|
Part B: Change from Baseline in QTc interval
Tidsramme: 30 minutes pre-dose and up to 2 hours post-dose
|
30 minutes pre-dose and up to 2 hours post-dose
|
|
Part C: Number of Participants Experiencing an Adverse Event (AE)
Tidsramme: Up to 18 weeks (six 3-week cycles)
|
Up to 18 weeks (six 3-week cycles)
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Number of participants whose best response is partial response (PR) or complete response (CR)
Tidsramme: Week 6
|
Week 6
|
|
Progression free survival
Tidsramme: Week 6
|
Week 6
|
|
Disease control rate
Tidsramme: Week 6
|
Week 6
|
|
Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)
Tidsramme: Day 1
|
Day 1
|
|
Part B: PK of Vintafolide Metabolites, including AUC and Cmax
Tidsramme: Day 1
|
Day 1
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
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. desember 2012
Primær fullføring (Faktiske)
1. september 2014
Studiet fullført (Faktiske)
1. september 2014
Datoer for studieregistrering
Først innsendt
17. september 2012
Først innsendt som oppfylte QC-kriteriene
17. september 2012
Først lagt ut (Anslag)
20. september 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
10. februar 2015
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. februar 2015
Sist bekreftet
1. februar 2015
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 8109-001
- 2012-002799-14 (EudraCT-nummer)
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