Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma
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
2 other identifiers
interventional
89
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2011
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 23, 2011
CompletedFirst Posted
Study publicly available on registry
September 22, 2011
CompletedStudy Start
First participant enrolled
October 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2018
CompletedAugust 29, 2018
August 1, 2018
4.5 years
August 23, 2011
August 28, 2018
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors
Approximately one year
Adverse events as a measure of the safety and tolerability profile of pazopanib in combination with GSK1120212 in patients with solid tumors
Approximately two years
Secondary Outcomes (4)
Objective response rate at six months in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at the MTD
Approximately one year
Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.
Approximately one year
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
Approximately one year
PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma
Approximately one year
Study Arms (1)
Pazopanib and GSK1120212
EXPERIMENTALTreatment 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkinslead
- National Comprehensive Cancer Networkcollaborator
- Novartiscollaborator
Study Sites (2)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nilo Azad, MD
Johns Hopkins University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 23, 2011
First Posted
September 22, 2011
Study Start
October 1, 2011
Primary Completion
April 1, 2016
Study Completion
August 1, 2018
Last Updated
August 29, 2018
Record last verified: 2018-08