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

NCT00876109 | Completed Phase 1

• 2 other identifiers: GDC4255gGO01300
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

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.

Conditions

Solid Cancers

Keywords

Metastatic Solid Tumors; PI3K; PI3K Inhibitors

Outcome Measures

Primary Outcomes (7)

• 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)

• 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)

• 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)

• 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)

• Percentage of Participants with Dose-Limiting Toxicities (DLTs)

  Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36

• 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)

• 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)

Secondary Outcomes (3)

• 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)

• 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)

• 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)

Study Arms (3)

Group A: GDC-0941 QD Dose Escalation

EXPERIMENTAL

Participants will receive GDC-0941 for up to 1 year, administered orally QD at a starting dose of 15 milligrams (mg).

Drug: GDC-0941

Group B: GDC-0941 BID Dose Escalation

EXPERIMENTAL

Participants will receive GDC-0941 for up to 1 year, administered orally BID at a starting dose determined from Group A assessments.

Drug: GDC-0941

Group C: GDC-0941 QD or BID Expansion

EXPERIMENTAL

Participants will receive GDC-0941 for up to 1 year, administered orally QD or BID. The dose/regimen will be determined on the basis of data from Groups A and B.

Drug: GDC-0941

Interventions

GDC-0941 DRUG

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.

Also known as: PI3-Kinase Inhibitor

Group A: GDC-0941 QD Dose Escalation; Group B: GDC-0941 BID Dose Escalation; Group C: GDC-0941 QD or BID Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (3)

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

Boston, Massachusetts, 02215, United States

Location

Unknown Facility

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Interventions

2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine

Study Officials

• Jerry Hsu, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: April 6, 2009
• Study Start: October 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: November 1, 2013
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (3)