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This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors

6 oktober 2015 bijgewerkt door: 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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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

Ingrijpend

Inschrijving (Werkelijk)

35

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Australië
    • Victoria
      • East Melbourne, Victoria, Australië, 3002
        • Pfizer Investigational Site
  • Verenigde Staten
    • California
      • Santa Monica, California, Verenigde Staten, 90404
        • Pfizer Investigational Site
    • Colorado
      • Aurora, Colorado, Verenigde Staten, 80045
        • Pfizer Investigational Site

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:

  • 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.

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: 1
Geneesmiddel: PF-03758309
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT)
Tijdsspanne: 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])
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
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])

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants With Objective Response
Tijdsspanne: 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
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.
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
Time to Tumor Progression (TTP)
Tijdsspanne: 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
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])
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
Duration of Response
Tijdsspanne: 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
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.
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
Maximum Observed Plasma Concentration (Cmax)
Tijdsspanne: 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
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
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tijdsspanne: 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
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
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Tijdsspanne: 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
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
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
Area Under the Concentration-Time Curve From Time 0 to 12 Hours Post Morning Dose [AUC(0-12)]
Tijdsspanne: pre-dose and 12 hours post morning dose
pre-dose and 12 hours post morning dose
Minimum Observed Plasma Trough Concentration (Cmin)
Tijdsspanne: 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
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
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Tijdsspanne: 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
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
PAK (p21 Activated Kinase)-Related Pathway Molecule Expression Modulation by PF-03758309 in Tumor and Surrogate Tissue
Tijdsspanne: 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
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
Baseline Tumor Expression of PAK-related Pathway Molecules and Other Known Biomarkers
Tijdsspanne: Baseline
Baseline

Medewerkers en onderzoekers

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

Sponsor

Pfizer

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.

Algemene publicaties

Nuttige links

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 september 2009

Primaire voltooiing (Werkelijk)

1 december 2011

Studie voltooiing (Werkelijk)

1 december 2011

Studieregistratiedata

Eerst ingediend

30 juni 2009

Eerst ingediend dat voldeed aan de QC-criteria

2 juli 2009

Eerst geplaatst (Schatting)

3 juli 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

28 oktober 2015

Laatste update ingediend die voldeed aan QC-criteria

6 oktober 2015

Laatst geverifieerd

1 oktober 2015

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • B1301001

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