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

This study is currently recruiting participants.
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborators:
National Comprehensive Cancer Network
GlaxoSmithKline
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01438554
First received: August 23, 2011
Last updated: March 23, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Solid Tumors
Thyroid Cancer
Soft-tissue Sarcoma
Cholangiocarcinoma
Drug: Pazopanib
Drug: GSK1120212
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors [ Time Frame: Approximately one year ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD. [ Time Frame: Approximately one year ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma [ Time Frame: Approximately one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 111
Study Start Date: October 2011
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Dose escalation cohort for all solid tumors is complete and closed to enrollment. For the expansion cohorts, patients must have: advanced, inoperable differentiated thyroid cancer (DTC), soft-tissue sarcoma or cholangiocarcinoma. 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01438554

Contacts
Contact: Kathy Elza-Brown, RN 410-502-5140 kelzabr1@jhmi.edu
Contact: Nilo Azad, MD 410-614-9169 nazad2@jhmi.edu

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Comprehensive Cancer Network
GlaxoSmithKline
Investigators
Principal Investigator: Nilo Azad, MD Johns Hopkins University
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01438554     History of Changes
Other Study ID Numbers: J1162, NA_00048646
Study First Received: August 23, 2011
Last Updated: March 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cholangiocarcinoma
Thyroid Neoplasms
Thyroid Diseases
Neoplasms
Sarcoma
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on April 16, 2014