Back to resultsPhase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma
Primary Purpose
Solid Tumors, Thyroid Cancer, Soft-tissue Sarcoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pazopanib
GSK1120212
Sponsored by
About this trial
This is an interventional other trial for Solid Tumors
Eligibility Criteria
Inclusion Criteria:
- Dose escalation cohort for all solid tumors is closed to enrollment.
- Expansion cohorts: Soft-tissue sarcoma, cholangiocarcinoma, and differentiated thyroid cancer (DTC) cohorts are closed to enrollment. Patients in the DTC cohort must have disease that is able to be biopsied.
- Must have measurable disease.
- Tumor progression in the 6-month period prior to study drug initiation.
- DTC patients: must have radioiodine non-avid lesions, OR radioiodine avid lesions that have not responded to treatment with radioactive iodine.
- ECOG performance status less than or equal to 1.
- Life expectancy >3 months.
- Blood pressure <140 mmHg and <90 mmHg.
- LVEF is >= 50%
- Must be able to swallow pills.
Exclusion Criteria:
- Chemotherapy, radiotherapy, other investigational therapy, or major surgery within 4 weeks.
- Sarcoma and cholangiocarcinoma ONLY: Prior VEGF-targeted TKI therapy.
- Pregnant or currently breastfeeding.
- Unresolved toxicity greater than grade 1.
- Evidence of active hepatitis or HIV.
- Significant cardiovascular disease.
- Taking medications known to be strong inducers or inhibitors of CYP3A enzymes.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
- History of gastrointestinal condition causing malabsorption or obstruction.
- Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein thrombosis (DVT) within past 6 months.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase risk of pulmonary hemorrhage.
- Hemoptysis within 6 months of starting treatment.
- History of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR as assessed by ophthalmic exam.
- Known brain mets that are not stable for at least 8 weeks prior to treatment, or patient is on glucocorticoids for brain mets.
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib and GSK1120212
Arm Description
Treatment will be administered on an outpatient basis. Both drugs are taken orally. Each cycle lasts 28 days. The doses of each drug will depend on when patient enters study.
Outcomes
Primary Outcome Measures
Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors
Adverse events as a measure of the safety and tolerability profile of pazopanib in combination with GSK1120212 in patients with solid tumors
Secondary Outcome Measures
Objective response rate at six months in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at the MTD
Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.
Correlation of PK data with radiographic response, PD markers, and the impact of tumor histologic subtype and tumor genotype on radiographic response for patients with advanced thyroid cancer
PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma
Full Information
NCT ID
NCT01438554
First Posted
August 23, 2011
Last Updated
August 28, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Comprehensive Cancer Network, Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01438554
Brief Title
Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma
Official Title
Phase I Study Determining the Safety and Tolerability of Combination Therapy With Pazopanib, a VEGFR/PDGFR/Raf Inhibitor, and GSK1120212, a MEK Inhibitor, in Advanced Solid Tumors Enriched With Patients With Advanced Differentiated Thyroid Cancer, Soft Tissue Sarcoma, and Cholangiocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2011 (Actual)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
August 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Comprehensive Cancer Network, Novartis
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and toxicity of the combination of pazopanib and GSK1120212 in patients with solid tumors and identify the maximum tolerated dose (MTD) of this combination for phase II study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Thyroid Cancer, Soft-tissue Sarcoma, Cholangiocarcinoma
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib and GSK1120212
Arm Type
Experimental
Arm Description
Treatment will be administered on an outpatient basis. Both drugs are taken orally. Each cycle lasts 28 days. The doses of each drug will depend on when patient enters study.
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
Votrient
Intervention Type
Drug
Intervention Name(s)
GSK1120212
Other Intervention Name(s)
Trametinib, Mekinist
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors
Time Frame
Approximately one year
Title
Adverse events as a measure of the safety and tolerability profile of pazopanib in combination with GSK1120212 in patients with solid tumors
Time Frame
Approximately two years
Secondary Outcome Measure Information:
Title
Objective response rate at six months in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at the MTD
Time Frame
Approximately one year
Title
Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.
Time Frame
Approximately one year
Title
Correlation of PK data with radiographic response, PD markers, and the impact of tumor histologic subtype and tumor genotype on radiographic response for patients with advanced thyroid cancer
Time Frame
Approximately one year
Title
PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma
Time Frame
Approximately one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Dose escalation cohort for all solid tumors is closed to enrollment.
Expansion cohorts: Soft-tissue sarcoma, cholangiocarcinoma, and differentiated thyroid cancer (DTC) cohorts are closed to enrollment. Patients in the DTC cohort must have disease that is able to be biopsied.
Must have measurable disease.
Tumor progression in the 6-month period prior to study drug initiation.
DTC patients: must have radioiodine non-avid lesions, OR radioiodine avid lesions that have not responded to treatment with radioactive iodine.
ECOG performance status less than or equal to 1.
Life expectancy >3 months.
Blood pressure <140 mmHg and <90 mmHg.
LVEF is >= 50%
Must be able to swallow pills.
Exclusion Criteria:
Chemotherapy, radiotherapy, other investigational therapy, or major surgery within 4 weeks.
Sarcoma and cholangiocarcinoma ONLY: Prior VEGF-targeted TKI therapy.
Pregnant or currently breastfeeding.
Unresolved toxicity greater than grade 1.
Evidence of active hepatitis or HIV.
Significant cardiovascular disease.
Taking medications known to be strong inducers or inhibitors of CYP3A enzymes.
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
History of gastrointestinal condition causing malabsorption or obstruction.
Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein thrombosis (DVT) within past 6 months.
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase risk of pulmonary hemorrhage.
Hemoptysis within 6 months of starting treatment.
History of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR as assessed by ophthalmic exam.
Known brain mets that are not stable for at least 8 weeks prior to treatment, or patient is on glucocorticoids for brain mets.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nilo Azad, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma
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