Clinical trial NCT00968981: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Keywords: Hedgehog
BCC
basal cell carcinoma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-08-31
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449
timeFrame: 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
measure: Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough)
timeFrame: 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
measure: Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15
timeFrame: 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
measure: Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449
timeFrame: 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
measure: Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449
timeFrame: 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
measure: Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449
timeFrame: 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
measure: Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449
timeFrame: 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1
Secondary outcomes:
measure: Percentage of Participants With Disease Progression or Death
timeFrame: Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
measure: Percentage of Participants With a Response by Best Overall Response (BOR)
timeFrame: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
measure: Progression-Free Survival (PFS) Time
timeFrame: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
measure: Duration of Response (DR)
timeFrame: Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Jennifer Low, M.D.
role: STUDY_DIRECTOR
References:
citation: Jia G, Chandriani S, Abbas AR, DePianto DJ, N'Diaye EN, Yaylaoglu MB, Moore HM, Peng I, DeVoss J, Collard HR, Wolters PJ, Egen JG, Arron JR. CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis. Thorax. 2017 Sep;72(9):780-787. doi: 10.1136/thoraxjnl-2015-207682. Epub 2017 Mar 1.