Phase 1
Completed N=67
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
Solid Cancers
Source: ClinicalTrials.gov NCT00968981 ↗
Enrolled (actual)
67
Serious AEs
34.9%
Results posted
Dec 2015
Primary outcomePrimary: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449 — 24; 72; 15; 74 hours
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449 |
24; 72; 15; 74; 74; 24 | — |
| PRIMARY Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough) |
0; 1; 4; 0; 6; 9 | — |
| PRIMARY Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15 |
1.23; 0.87; 0.54; 1.34; 0.58; 0.20 | — |
| PRIMARY Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449 |
28; 26.1; 16.9; 0.163; 0.088; 0.0489 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449 |
7.09; 8.08; 7.29; 30.4; 29.5; 21.2 | — |
| PRIMARY Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449 |
130.88; 129.44; 126.05; 696; 595; 455 | — |
| PRIMARY Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449 |
431.20; 478.38; 453.14; 4834.06; 4302.84; 2935.33 | — |
| PRIMARY Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449 |
48; 48 | — |
| SECONDARY Percentage of Participants With Disease Progression or Death |
52.9; 75.0; 40.0 | — |
| SECONDARY Percentage of Participants With a Response by Best Overall Response (BOR) |
0.0; 0.0; 0.0; 7.7; 0.0; 0.0 | — |
| SECONDARY Progression-Free Survival (PFS) Time |
1.9; 1.9; 2.2 | — |
| SECONDARY Duration of Response (DR) |
— | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT00968981). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.