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

Johns Hopkins Medicine

Status and phase: Completed; Phase 1

Conditions: Soft-tissue Sarcoma; Cholangiocarcinoma; Thyroid Cancer; Solid Tumors

Treatments: Drug: Pazopanib; Drug: GSK1120212

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT01438554

J1162

NA_00048646 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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89 participants in 1 patient group

Pazopanib and GSK1120212

Experimental group

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.

Treatment:

Drug: GSK1120212

Drug: Pazopanib