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

Genentech

Status and phase: Completed; Phase 1

Conditions: Solid Cancers

Treatments: Drug: GDC-0449

Study type: Interventional

Funder types: Industry

Identifiers

NCT00968981

SHH4610g

Details and patient eligibility

About

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.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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67 participants in 3 patient groups

A

Experimental group

Treatment:

Drug: GDC-0449

B

Experimental group

Treatment:

Drug: GDC-0449

C

Experimental group

Treatment:

Drug: GDC-0449