Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01438554
• Other study ID #: J1162
• Secondary ID: NA_00048646
• Status: Completed
• Phase: Phase 1
• Start date: October 2011
• Est. completion date: August 2018

Study information

• Verified date: August 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: August 2018
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Sarcoma
• Soft-tissue Sarcoma
• Solid Tumors
• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Pazopanib

• GSK1120212

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Comprehensive Cancer Network, Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors		Approximately one year
Primary	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	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
Secondary	Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.		Approximately one year
Secondary	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
Secondary	PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma		Approximately one year