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

August 28, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

89

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Votrient
Drug: GSK1120212
Other Names:
  • Mekinist
  • Trametinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors
Time Frame: Approximately one year
Approximately one year
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
Approximately two years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Approximately one year
Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD.
Time Frame: Approximately one year
Approximately one year
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
Approximately one year
PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma
Time Frame: Approximately one year
Approximately one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Novartis
National Comprehensive Cancer Network

Investigators

  • Principal Investigator: Nilo Azad, MD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2011

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

August 23, 2011

First Submitted That Met QC Criteria

September 21, 2011

First Posted (Estimate)

September 22, 2011

Study Record Updates

Last Update Posted (Actual)

August 29, 2018

Last Update Submitted That Met QC Criteria

August 28, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J1162
  • NA_00048646 (Other Identifier: JHMIRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cholangiocarcinoma

Clinical Trials on Pazopanib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Poland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe