A Study Evaluating GDC-0980 Administered Once Daily in Patients With Refractory Solid Tumors or Non-Hodgkin's Lymphoma
Primary Purpose
Non-Hodgkin's Lymphoma, Solid Cancers
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GDC-0980
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma, Solid Cancers focused on measuring NHL, Tumors, Carcinogenic Tumors
Eligibility Criteria
Inclusion Criteria:
- Histologically documented, incurable, locally advanced or metastatic solid malignancies, or NHL without leukemic phase, that has progressed despite standard of care therapy or for which there is no standard therapy of proven clinical benefit
- ECOG performance status of 0 or 1 at screening
- Evaluable or measurable disease per RECIST and/or the following: prostate cancer patients with non-measurable disease are eligible if they have two rising prostate-specific antigen (PSA) levels that meet the PSA Working Group criteria for progression prior to initiation of study treatment; ovarian cancer patients with non-measurable disease are eligible if they have two rising CA-125 levels greater than the ULN >= 2 weeks apart prior to initiation of study treatment.
- Life expectancy >=12 weeks
- Adequate hematologic and organ function within 14 days before initiation of GDC-0980
- 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
- Grade >= 2 hypercholesterolemia or hypertriglyceridemia
- Ejection fraction that is <50% or below the LLN (whichever is higher), as determined by echocardiogram or MUGA scan
- DLCO < 50% of predicted value corrected for hemoglobin and alveolar volume prior to initiation of GDC-0980
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Known untreated malignancies of the brain or spinal cord, or treated brain metastases that are not radiographically stable for >= 3 months
- Active congestive heart failure or ventricular arrhythmia requiring medication
- Active infection requiring IV antibiotics
- Requirement for any daily supplemental oxygen
- Uncontrolled hypomagnesemia
- Hypercalcemia requiring continued use of bisphosphonate therapy
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Uncontrolled ascites requiring frequent paracentesis
- Known HIV infection
- Any other diseases, active or controlled 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
- Significant traumatic injury within 4 weeks of Day 1
- Major surgical procedure within 4 weeks prior to initiation of GDC-0980
- For all patients participating in Stage 2: Prior treatment with any PI3K inhibitor, mTOR inhibitor or dual PI3K/mTOR inhibitor. For HNSCC patients, this restriction applies only to any PI3K inhibitor, mTOR inhibitor, or dual PI3K/mTOR inhibitor used in the palliative setting.
- Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives, or GnRH agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 3 weeks prior to initiation of GDC-0980
- Palliative radiation to bony metastases within 2 weeks prior to initiation of GDC-0980
- Need for chronic corticosteroid therapy of >= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant
- Treatment with an investigational agent within 4 weeks prior to initiation of GDC-0980
- Unresolved toxicity from prior therapy except for alopecia and Grade 1 peripheral neuropathy
- Pregnancy or lactation
- For patients participating in DCE-MRI assessments, any contraindication to MRI examination
- For patients with advanced solid tumors or NHL participating in the PPI-effect assessment: Known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Occurrence of adverse events
Occurrence of dose-limiting toxicities
PK parameters after doses of GDC-0980
Occurrence of Grade 3 and 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0980
Secondary Outcome Measures
Best overall response, duration of objective response, and progression-free survival for patients with measurable disease
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00854152
Brief Title
A Study Evaluating GDC-0980 Administered Once Daily in Patients With Refractory Solid Tumors or Non-Hodgkin's Lymphoma
Official Title
An Open-label, Phase I, Dose-Escalation Study Evaluating the Safety, Tolerability, and Maximally Tolerated Dose of GDC-0980 Administered Once Daily in Patients With Refractory Solid Tumors and Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This is an open-label, multicenter, Phase I study to evaluate the safety, tolerability, and pharmacokinetics of escalating oral doses of GDC-0980 administered to patients with incurable, locally advanced or metastatic solid malignancy or NHL that has progressed or failed to respond to at least one prior regimen or for which there is no standard therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Solid Cancers
Keywords
NHL, Tumors, Carcinogenic Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GDC-0980
Intervention Description
Escalating repeating dose
Primary Outcome Measure Information:
Title
Occurrence of adverse events
Time Frame
Length of study
Title
Occurrence of dose-limiting toxicities
Time Frame
Length of study
Title
PK parameters after doses of GDC-0980
Time Frame
Length of study
Title
Occurrence of Grade 3 and 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0980
Time Frame
Length of study
Secondary Outcome Measure Information:
Title
Best overall response, duration of objective response, and progression-free survival for patients with measurable disease
Time Frame
Length of study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically documented, incurable, locally advanced or metastatic solid malignancies, or NHL without leukemic phase, that has progressed despite standard of care therapy or for which there is no standard therapy of proven clinical benefit
ECOG performance status of 0 or 1 at screening
Evaluable or measurable disease per RECIST and/or the following: prostate cancer patients with non-measurable disease are eligible if they have two rising prostate-specific antigen (PSA) levels that meet the PSA Working Group criteria for progression prior to initiation of study treatment; ovarian cancer patients with non-measurable disease are eligible if they have two rising CA-125 levels greater than the ULN >= 2 weeks apart prior to initiation of study treatment.
Life expectancy >=12 weeks
Adequate hematologic and organ function within 14 days before initiation of GDC-0980
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
Grade >= 2 hypercholesterolemia or hypertriglyceridemia
Ejection fraction that is <50% or below the LLN (whichever is higher), as determined by echocardiogram or MUGA scan
DLCO < 50% of predicted value corrected for hemoglobin and alveolar volume prior to initiation of GDC-0980
Malabsorption syndrome or other condition that would interfere with enteral absorption
Known untreated malignancies of the brain or spinal cord, or treated brain metastases that are not radiographically stable for >= 3 months
Active congestive heart failure or ventricular arrhythmia requiring medication
Active infection requiring IV antibiotics
Requirement for any daily supplemental oxygen
Uncontrolled hypomagnesemia
Hypercalcemia requiring continued use of bisphosphonate therapy
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Uncontrolled ascites requiring frequent paracentesis
Known HIV infection
Any other diseases, active or controlled 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
Significant traumatic injury within 4 weeks of Day 1
Major surgical procedure within 4 weeks prior to initiation of GDC-0980
For all patients participating in Stage 2: Prior treatment with any PI3K inhibitor, mTOR inhibitor or dual PI3K/mTOR inhibitor. For HNSCC patients, this restriction applies only to any PI3K inhibitor, mTOR inhibitor, or dual PI3K/mTOR inhibitor used in the palliative setting.
Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives, or GnRH agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 3 weeks prior to initiation of GDC-0980
Palliative radiation to bony metastases within 2 weeks prior to initiation of GDC-0980
Need for chronic corticosteroid therapy of >= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant
Treatment with an investigational agent within 4 weeks prior to initiation of GDC-0980
Unresolved toxicity from prior therapy except for alopecia and Grade 1 peripheral neuropathy
Pregnancy or lactation
For patients participating in DCE-MRI assessments, any contraindication to MRI examination
For patients with advanced solid tumors or NHL participating in the PPI-effect assessment: Known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mika Derynck, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
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A Study Evaluating GDC-0980 Administered Once Daily in Patients With Refractory Solid Tumors or Non-Hodgkin's Lymphoma
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