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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00876109
First received: March 13, 2009
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Solid Cancers
Drug: GDC-0941
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Maximum Observed Concentration (Cmax) of GDC-0941 [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-Life (t1/2) of GDC-0941 [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Area Under the Concentration-Time Curve (AUC) of GDC-0941 [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Grade 3 or 4 Abnormalities in Safety-Related Laboratory Parameters [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Time of Maximum Observed Concentration (Tmax) of GDC-0941 [ Time Frame: 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of Objective Response According to RECIST [ Time Frame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall) ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) According to RECIST [ Time Frame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall) ] [ Designated as safety issue: No ]
  • Percentage of Participants by Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall) ] [ Designated as safety issue: No ]

Enrollment: 108
Study Start Date: October 2007
Study Completion Date: November 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: GDC-0941 QD Dose Escalation
Participants will receive GDC-0941 for up to 1 year, administered orally QD at a starting dose of 15 milligrams (mg).
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.
Other Name: PI3-Kinase Inhibitor
Experimental: Group B: GDC-0941 BID Dose Escalation
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
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.
Other Name: PI3-Kinase Inhibitor
Experimental: Group C: GDC-0941 QD or BID Expansion
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
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.
Other Name: PI3-Kinase Inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00876109

Locations
United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, Michigan
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Jerry Hsu, M.D. Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00876109     History of Changes
Other Study ID Numbers: GDC4255g  GO01300 
Study First Received: March 13, 2009
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
Metastatic Solid Tumors
PI3K
PI3K Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016