Clinical trial NCT00876109: A Study of GDC-0941 in Participants With Locally Advanced or Metastatic Solid Tumors for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable
Official title: An Open-Label, Phase I, Dose-Escalation Study Evaluating Two Dosing Schedules of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Keywords: Metastatic Solid Tumors
PI3K
PI3K Inhibitors
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-04-06
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of orally administered GDC-0941 administered once daily (QD) and twice daily (BID) in the treatment of advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

* Participants with histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed or failed to respond to at least one prior regimen, and who are not candidates for regimens known to provide clinical benefit
* Evaluable or measurable disease per RECIST
* Life expectancy of greater than or equal to (\>/=) 12 weeks
* Documented willingness to use an effective means of contraception (for both men and women) while participating in the study

Exclusion Criteria:

* Leptomeningeal disease as the only manifestation of the current malignancy
* History of Type 1 or 2 diabetes mellitus requiring regular medication
* Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Known untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for \>/=3 months
* Active congestive heart failure or ventricular arrhythmia requiring medication
* Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to enrollment
* Active infection requiring intravenous (IV) antibiotics
* Requirement for any daily supplemental oxygen
* Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit of normal (LLN), or hypercalcemia above the upper limit of normal (ULN) for the institution despite adequate electrolyte supplementation or management
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Known human immunodeficiency virus (HIV) infection
* Any other diseases, active or uncontrolled pulmonary dysfunction, 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 participant at high risk from treatment complications
* Significant traumatic injury within 3 weeks before Day 1
* Major surgical procedure within 4 weeks prior to initiation of study treatment
* Treatment with chemotherapy, hormonal therapy (except gonadotropin releasing hormone \[GnRH\] agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, or radiation therapy (except palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment
* Palliative radiation to bony metastases within 2 weeks prior to initiation of study treatment
* Need for chronic corticosteroid therapy for greater than (\>) 7 days

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of GDC-0941
timeFrame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
measure: Terminal Elimination Half-Life (t1/2) of GDC-0941
timeFrame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
measure: Area Under the Concentration-Time Curve (AUC) of GDC-0941
timeFrame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
measure: Percentage of Participants with Adverse Events
timeFrame: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36
measure: Percentage of Participants with Grade 3 or 4 Abnormalities in Safety-Related Laboratory Parameters
timeFrame: Visits at Baseline and during treatment on Days 1, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
measure: Time of Maximum Observed Concentration (Tmax) of GDC-0941
timeFrame: Pre-dose (5 minutes [min]) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 hours [h]) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Secondary outcomes:
measure: Duration of Objective Response According to RECIST
timeFrame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
measure: Progression-Free Survival (PFS) According to RECIST
timeFrame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
measure: Percentage of Participants by Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
Study officials:
affiliation: Genentech, Inc.
name: Jerry Hsu, M.D.
role: STUDY_DIRECTOR
References: