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A Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists

8. Juni 2017 aktualisiert von: Genentech, Inc.

A Phase Ib, Open-Label, Dose-Scheduling Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists

This is a two stage, Phase Ib study designed to describe the pharmacokinetics of GDC-0449 in patients with advanced solid tumors that are refractory to treatment or for whom no standard therapy exists.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Tatsächlich)

67

Phase

  • Phase 1

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria

  • Histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed after first-line and second-line therapy (if there is a second-line therapy that has been shown to provide clinical benefit); patients with basal cell carcinoma will be excluded from this study unless they do not qualify for another open GDC-0449 clinical trial
  • For patients with disease that is evaluable by physical examination only, diagnosis must also include biomarker confirmation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Documented negative pregnancy test for women of childbearing potential and agreement to use an effective form of contraception for the duration of the study
  • Adequate hematopoietic capacity
  • Adequate hepatic function
  • Adequate renal function
  • At least 3 weeks since last chemotherapy, investigational agent, radiation therapy, or major surgical procedure and recovery to pre-treatment baseline or stabilization of all treatment-related toxicities

Exclusion Criteria

  • Known, untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for ≥ 3 months
  • Active infection requiring intravenous (IV) antibiotics
  • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis
  • Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g., gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
  • Pregnant or lactating
  • Treatment with excluded medications, including strong CYP450 inhibitors and inducers

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: EIN
Arzneimittel: GDC-0449
Daily oral repeating dose
Arzneimittel: GDC-0449
Three times weekly oral repeating dose
Arzneimittel: GDC-0449
Once weekly oral repeating dose
Experimental: B
Arzneimittel: GDC-0449
Daily oral repeating dose
Arzneimittel: GDC-0449
Three times weekly oral repeating dose
Arzneimittel: GDC-0449
Once weekly oral repeating dose
Experimental: C
Arzneimittel: GDC-0449
Daily oral repeating dose
Arzneimittel: GDC-0449
Three times weekly oral repeating dose
Arzneimittel: GDC-0449
Once weekly oral repeating dose

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough)
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Percent change = ([trough concentration on Day 15 minus trough concentration on Day 57] divided by trough concentration on Day 15) multiplied by 100.
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Ratio = trough concentration on Day 57 divided by trough concentration on Day 15. If the ratio of total and unbound trough GDC-0449 concentration between Day 57 to Day 15 is less than 1, then it indicates reduction in total and unbound trough GDC-0449 concentration between Day 15 to Day 57.
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Plasma GDC-0449 concentrations were reported in nanogram per milliliter (ng/mL) units and converted to micromolar (mcM) units using the molecular weight (421.30 grams per mole [g/mol]) prior to PK analysis. Css was calculated for Days 28 to 56.
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449
Zeitfenster: 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
Plasma GDC-0449 concentrations were reported in ng/mL units and converted to mcM units using the molecular weight (421.30 g/mol) prior to PK analysis.
0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin). Below the limit of quantitation (BLQ) values at pre-dose were considered as zero for PK analysis.
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449
Zeitfenster: Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin). BLQ values at pre-dose were considered as zero for PK analysis.
Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449
Zeitfenster: 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1
0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Percentage of Participants With Disease Progression or Death
Zeitfenster: Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
Disease progression (assessed by Response Evaluation Criteria in Solid Tumors [RECIST]) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing non target lesions.
Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
Percentage of Participants With a Response by Best Overall Response (BOR)
Zeitfenster: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
BOR was defined as the best overall response observed during the treatment period according to RECIST. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. Progressive disease (PD): at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Progression-Free Survival (PFS) Time
Zeitfenster: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
PFS defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by the investigator review of tumor assessments using RECIST, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).
Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Duration of Response (DR)
Zeitfenster: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
DR during first line therapy is defined as the time from when response (complete response [CR] or partial response [PR]) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only be calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow up for progression of disease during first line therapy. CR: disappearance of all target lesions (TLs) with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters. PR: at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum diameters. DR was not calculated as only 1 responding participant reached their response at the last scheduled response assessment, hence follow-up data are not available.
Screening Day 57, and every 8 weeks thereafter up to 52 weeks

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Genentech, Inc.

Ermittler

  • Studienleiter: Jennifer Low, M.D., Genentech, Inc.

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

1. September 2009

Primärer Abschluss (Tatsächlich)

1. Oktober 2010

Studienabschluss (Tatsächlich)

1. Oktober 2010

Studienanmeldedaten

Zuerst eingereicht

28. August 2009

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

28. August 2009

Zuerst gepostet (Schätzen)

31. August 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

11. Juli 2017

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

8. Juni 2017

Zuletzt verifiziert

1. Juni 2017

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Andere Studien-ID-Nummern

  • SHH4610g

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