- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00932126
This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors
6. oktober 2015 oppdatert av: Pfizer
Phase 1, Open Label, Dose-Escalation, Safety, Pharmacokinetic And Pharmacodynamic Study Of Single Agent PF-03758309, An Oral PAK4 Inhibitor, In Patients With Advanced Solid Tumors
This is the first study using PF-03758309, an oral compound, in patients with advanced solid tumors.
In this study different doses of PF-03758309 will be administered to different groups of patients.
The study will assess the compound's safety, the blood levels of PF-03758309 during the treatment and the effect of the compound on the tumor cells.
Studieoversikt
Status
Avsluttet
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The study was prematurely terminated on 26Jul2011 due to the undesirable PK characteristics of PF-03758309 and the lack of an observed dose-response relationship.
There were no safety concerns that contributed to the study termination.
Studietype
Intervensjonell
Registrering (Faktiske)
35
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Victoria
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East Melbourne, Victoria, Australia, 3002
- Pfizer Investigational Site
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California
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Santa Monica, California, Forente stater, 90404
- Pfizer Investigational Site
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Colorado
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Aurora, Colorado, Forente stater, 80045
- Pfizer Investigational Site
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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:
- Advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
- ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) must be 0 or 1.
- Adequate bone marrow, liver and kidney function.
Exclusion Criteria:
- Patients with known brain metastases.
- Previous high dose chemotherapy requiring stem cell rescue.
- Prior irradiation to >25% of the bone marrow.
- Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV).
- Current active treatment in another clinical study.
- Pregnancy or breast feeding.
- Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment.
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 |
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Eksperimentell: 1
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Oral PF-03758309 will be administered in capsules (once or twice daily) until toxicity, progressive disease, or patient refusal to continue on therapy.
The starting dose is 1 mg once daily.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT)
Tidsramme: Baseline (up to 30 days prior to first study drug administration) till 28 days after the last treatment administration (end of Cycle 1 [28 days])
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DLT includes: Grade (GR) 4 neutropenia (NP) that persisted for >7 consecutive days; Febrile NP; GR3 NP infection; GR4 thrombocytopenia (TP); GR3 TP with bleeding; Any other GR>=3 toxicity not classified under Common Terminology Criteria for Adverse Events (CTCAE) blood or bone marrow (exception of nausea, vomiting, or diarrhea in subjects who received optimal treatment with antiemetics or anti-diarrheals); Failure to recover to an adequate condition to recommence study treatment after a 2-week delay; Failure to receive >= 80% of planned PF-03758309 dose due to study drug related toxicity
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Baseline (up to 30 days prior to first study drug administration) till 28 days after the last treatment administration (end of Cycle 1 [28 days])
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Number of Participants With Objective Response
Tidsramme: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST.
Confirmed CR defined as disappearance of all target lesions.
Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST.
Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
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Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Time to Tumor Progression (TTP)
Tidsramme: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first.
TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD])
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Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Duration of Response
Tidsramme: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer.
Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
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Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
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Maximum Observed Plasma Concentration (Cmax)
Tidsramme: predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tidsramme: predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Tidsramme: predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
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predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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Area Under the Concentration-Time Curve From Time 0 to 12 Hours Post Morning Dose [AUC(0-12)]
Tidsramme: pre-dose and 12 hours post morning dose
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pre-dose and 12 hours post morning dose
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Minimum Observed Plasma Trough Concentration (Cmin)
Tidsramme: predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Tidsramme: predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
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PAK (p21 Activated Kinase)-Related Pathway Molecule Expression Modulation by PF-03758309 in Tumor and Surrogate Tissue
Tidsramme: Screening, 0, 2, 4, and 72 hours post dose Cycle 2 Day 8. A 6th sample of hair follicle could be requested at 6 or 8 hours post-dose if necessary. For fresh tumor tissue, baseline and between Day 8 and 22 of Cycle 1 in participants with accessible tumors
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Screening, 0, 2, 4, and 72 hours post dose Cycle 2 Day 8. A 6th sample of hair follicle could be requested at 6 or 8 hours post-dose if necessary. For fresh tumor tissue, baseline and between Day 8 and 22 of Cycle 1 in participants with accessible tumors
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Baseline Tumor Expression of PAK-related Pathway Molecules and Other Known Biomarkers
Tidsramme: Baseline
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Baseline
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Samarbeidspartnere og etterforskere
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Sponsor
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Hjelpsomme linker
Studierekorddatoer
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Studer hoveddatoer
Studiestart
1. september 2009
Primær fullføring (Faktiske)
1. desember 2011
Studiet fullført (Faktiske)
1. desember 2011
Datoer for studieregistrering
Først innsendt
30. juni 2009
Først innsendt som oppfylte QC-kriteriene
2. juli 2009
Først lagt ut (Anslag)
3. juli 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
28. oktober 2015
Siste oppdatering sendt inn som oppfylte QC-kriteriene
6. oktober 2015
Sist bekreftet
1. oktober 2015
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- B1301001
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