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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01438554
Recruitment Status : Completed
First Posted : September 22, 2011
Last Update Posted : August 29, 2018
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Novartis
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumors Thyroid Cancer Soft-tissue Sarcoma Cholangiocarcinoma Drug: Pazopanib Drug: GSK1120212 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : October 2011
Actual Primary Completion Date : April 2016
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Pazopanib and GSK1120212
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.
 Drug: Pazopanib
Other Name: Votrient

Drug: GSK1120212
Other Names:
  • Trametinib
  • Mekinist


Outcome Measures
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Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors [ Time Frame: Approximately one year ]
  2. 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 Measures :
  1. 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 ]
  2. Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD. [ Time Frame: Approximately one year ]
  3. 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 ]
  4. PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma [ Time Frame: Approximately one year ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01438554


Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Comprehensive Cancer Network
Novartis
Investigators
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Principal Investigator: Nilo Azad, MD Johns Hopkins University
More Information
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01438554    
Other Study ID Numbers: J1162
NA_00048646 ( Other Identifier: JHMIRB )
First Posted: September 22, 2011    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Diseases
Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Sarcoma
 Cholangiocarcinoma
Endocrine System Diseases
Adenocarcinoma
Carcinoma
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action