Clinical trial NCT01438554: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Thyroid Cancer
Soft-tissue Sarcoma
Cholangiocarcinoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Novartis
First posted: 2011-09-22
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors
timeFrame: Approximately one year
measure: Adverse events as a measure of the safety and tolerability profile of pazopanib in combination with GSK1120212 in patients with solid tumors
timeFrame: Approximately two years
Secondary outcomes:
measure: Objective response rate at six months in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at the MTD
timeFrame: Approximately one year
measure: Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.
timeFrame: Approximately one year
measure: 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
timeFrame: Approximately one year
measure: PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma
timeFrame: Approximately one year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Johns Hopkins University
name: Nilo Azad, MD
role: PRINCIPAL_INVESTIGATOR
References: