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

Solid Cancers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00876109
• Other study ID #: GDC4255g
• Secondary ID: GO01300
• Status: Completed
• Phase: Phase 1
• First received: March 13, 2009
• Last updated: November 1, 2016
• Start date: October 2007
• Est. completion date: November 2013

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: November 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Cancers

Intervention

Drug:
• GDC-0941
GDC-0941 will be administered in escalating oral doses QD or BID in Groups A and B, respectively. In Group C, the dose/regimen will be determined on the basis of data from Groups A and B. The overall starting dose will be 15 mg administered in the first cohort enrolled in Group A.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax) of GDC-0941		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)	No
Primary	Terminal Elimination Half-Life (t1/2) of GDC-0941		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)	No
Primary	Area Under the Concentration-Time Curve (AUC) of GDC-0941		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)	No
Primary	Percentage of Participants with Adverse Events		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)	No
Primary	Percentage of Participants with Dose-Limiting Toxicities (DLTs)		Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36	No
Primary	Percentage of Participants with Grade 3 or 4 Abnormalities in Safety-Related Laboratory Parameters		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)	No
Primary	Time of Maximum Observed Concentration (Tmax) of GDC-0941		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)	No
Secondary	Duration of Objective Response According to RECIST		Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)	No
Secondary	Progression-Free Survival (PFS) According to RECIST		Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)	No
Secondary	Percentage of Participants by Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)		Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)	No