Study of GDC-0980 Versus Everolimus in Participants With Metastatic Renal Cell Carcinoma Who Have Progressed on or Following Vascular Endothelial Growth Factor- (VEGF) Targeted Therapy
Primary Purpose
Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Everolimus
GDC-0980
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically documented, incurable metastatic renal cell carcinoma with clear-cell component that progressed on or within 6 months of stopping VEGF-targeted therapy
- Disease that is measurable per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- Karnofsky performance status of greater than or equal to (>=) 70 percent (%)
- Adequate hematologic and end organ function
- For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use two effective forms of contraception and to continue its use for the duration of the study
Exclusion Criteria:
- Any anti-cancer therapy, including chemotherapy, biologic or other targeted therapy, herbal therapy, hormonal therapy, or radiotherapy, within 5 half-lives (for systemic agents) or 2 weeks, whichever is shorter, prior to Day 1. Certain forms of radiation therapy may be considered for pain palliation if participants are deriving benefit
- Previously established diagnosis of pulmonary fibrosis of any cause
- New York Heart Association (NYHA) Class II or greater congestive heart failure
- History of malabsorption syndrome or other condition that would interfere with enteral absorption
- Presence of positive test results for hepatitis B (hepatitis B [HB] surface antigen [HBsAg] and/or total HB core antibody [anti-HB-c; both tests are required]) or hepatitis C
- Known human immunodeficiency virus (HIV) infection
- Pregnancy, lactation, or breastfeeding
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 or anticipation of the need for major surgery during the course of study treatment
- Leptomeningeal disease as a manifestation of cancer
- History of other malignancies less than equal to <= 5 years of Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Need for current chronic corticosteroid therapy (>= 10 milligrams [mg] of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids for greater than [>] 7 days) or use of other immunosuppressant
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Everolimus
GDC-0980
Arm Description
Participants will receive everolimus (10 mg) orally daily until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Participants will receive GDC-0980 (40 mg) orally daily until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Outcomes
Primary Outcome Measures
DUration of progression-free survival (PFS) as assessed by the investigator using RECIST v1.1
Secondary Outcome Measures
Maximum plasma concentration (Cmax) of GDC-0980
Cmax of everolimus
Minimum plasma concentration (Cmin) of GDC-0980
Cmin of everolimus
Number of participants with adverse events
Number of participants with objective tumor response as assessed by the investigator using RECIST v1.1
Duration of objective tumour response as assessed by the investigator using RECIST v1.1
Duration of overall survival (OS)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01442090
Brief Title
Study of GDC-0980 Versus Everolimus in Participants With Metastatic Renal Cell Carcinoma Who Have Progressed on or Following Vascular Endothelial Growth Factor- (VEGF) Targeted Therapy
Official Title
A Phase II, Open-Label, Randomized Study of GDC-0980 Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma Who Have Progressed on or Following VEGF-Targeted Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
Study PIM4973g is a multicenter, international, open-label Phase II trial. Participants with metastatic renal cell carcinoma who have progressed on or after VEGF targeted therapy will be randomized in 1:1 to two groups either to receive daily GDC-0980 or everolimus orally.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
85 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Active Comparator
Arm Description
Participants will receive everolimus (10 mg) orally daily until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Arm Title
GDC-0980
Arm Type
Experimental
Arm Description
Participants will receive GDC-0980 (40 mg) orally daily until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
Everolimus will be administered orally at a 10 mg daily dose.
Intervention Type
Drug
Intervention Name(s)
GDC-0980
Intervention Description
GDC-0980 will be administered orally at a 40 mg daily dose.
Primary Outcome Measure Information:
Title
DUration of progression-free survival (PFS) as assessed by the investigator using RECIST v1.1
Time Frame
Baseline until disease progression or death, whichever occurred first (up to approximately 23 months)
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) of GDC-0980
Time Frame
pre-dose and 1, 2, 4 hours post-dose on Week 1 Day 1, Pre-dose on Week 1 Day 2, pre-dose and 2 hours post dose on Week 3 Day 1 and Week 9 Day 1, 48 hours after last dose (up to approximately 23 months)
Title
Cmax of everolimus
Time Frame
pre-dose and 2, hours post-dose on Week 1 Day 1 and Week 9 Day 1, 48 hours after last dose (up to approximately 23 months)\n
Title
Minimum plasma concentration (Cmin) of GDC-0980
Time Frame
pre-dose on Week 1 Day 1, Week 1 Day 2, Week 3 Day 1 and Week 9 Day 1
Title
Cmin of everolimus
Time Frame
pre-dose on Week 1 Day 1 and Week 9 Day 1
Title
Number of participants with adverse events
Time Frame
up to 30 days after end of treatment (approximately up to 23 months)
Title
Number of participants with objective tumor response as assessed by the investigator using RECIST v1.1
Time Frame
Baseline until disease progression or death, whichever occurred first (up to approximately 23 months)
Title
Duration of objective tumour response as assessed by the investigator using RECIST v1.1
Time Frame
Baseline until disease progression or death, whichever occurred first (up to approximately 23 months)
Title
Duration of overall survival (OS)
Time Frame
Baseline until death (up to approximately 45 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically documented, incurable metastatic renal cell carcinoma with clear-cell component that progressed on or within 6 months of stopping VEGF-targeted therapy
Disease that is measurable per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Karnofsky performance status of greater than or equal to (>=) 70 percent (%)
Adequate hematologic and end organ function
For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use two effective forms of contraception and to continue its use for the duration of the study
Exclusion Criteria:
Any anti-cancer therapy, including chemotherapy, biologic or other targeted therapy, herbal therapy, hormonal therapy, or radiotherapy, within 5 half-lives (for systemic agents) or 2 weeks, whichever is shorter, prior to Day 1. Certain forms of radiation therapy may be considered for pain palliation if participants are deriving benefit
Previously established diagnosis of pulmonary fibrosis of any cause
New York Heart Association (NYHA) Class II or greater congestive heart failure
History of malabsorption syndrome or other condition that would interfere with enteral absorption
Presence of positive test results for hepatitis B (hepatitis B [HB] surface antigen [HBsAg] and/or total HB core antibody [anti-HB-c; both tests are required]) or hepatitis C
Known human immunodeficiency virus (HIV) infection
Pregnancy, lactation, or breastfeeding
Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 or anticipation of the need for major surgery during the course of study treatment
Leptomeningeal disease as a manifestation of cancer
History of other malignancies less than equal to <= 5 years of Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Need for current chronic corticosteroid therapy (>= 10 milligrams [mg] of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids for greater than [>] 7 days) or use of other immunosuppressant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33908
Country
United States
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
City
Bordeaux
ZIP/Postal Code
33075
Country
France
City
Paris
ZIP/Postal Code
75908
Country
France
City
Villejuif
ZIP/Postal Code
94800
Country
France
City
Berlin
ZIP/Postal Code
10117
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
München
ZIP/Postal Code
81377
Country
Germany
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26951309
Citation
Powles T, Lackner MR, Oudard S, Escudier B, Ralph C, Brown JE, Hawkins RE, Castellano D, Rini BI, Staehler MD, Ravaud A, Lin W, O'Keeffe B, Wang Y, Lu S, Spoerke JM, Huw LY, Byrtek M, Zhu R, Ware JA, Motzer RJ. Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma. J Clin Oncol. 2016 May 10;34(14):1660-8. doi: 10.1200/JCO.2015.64.8808. Epub 2016 Mar 7.
Results Reference
derived
Learn more about this trial
Study of GDC-0980 Versus Everolimus in Participants With Metastatic Renal Cell Carcinoma Who Have Progressed on or Following Vascular Endothelial Growth Factor- (VEGF) Targeted Therapy
We'll reach out to this number within 24 hrs