Pazopanib in Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST)

A Phase II Study of Pazopanib in Patients With Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST)

This study is being done to gather information about the safety (any harmful effects) and effectiveness (usefulness) of Pazopanib in the treatment of Gastrointestinal Stroma Tumors (GIST) that cannot be treated by surgery or has spread to other organs. The Food and Drug Administration (FDA) have approved Pazopanib for the treatment of advanced kidney cancer but it is not approved for the treatment of GIST. The investigators hope to learn about the safety and usefulness (effectiveness) of Pazopanib for patients with GIST.

Primary Objective:

Non-progression rate based on RECIST criteria (CR+PR+SD)

Secondary Objectives:

• Response per Choi criteria
• 6 month progression-free survival
• Safety and tolerability

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor (GIST)
• Intervention / Treatment: Drug: Pazopanib

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute

Participation Criteria

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:

• Metastatic or unresectable gastrointestinal stromal tumor (GIST)
• Failure or intolerance to Imatinib and sunitinib
• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
• Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Measurable disease criteria by RECIST criteria
• Adequate organ system function as defined in protocol.
• A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant). This includes any female who has had:
• A hysterectomy
• A bilateral oophorectomy (ovariectomy)
• A bilateral tubal ligation
• Menopause
• Childbearing potential females must have a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agree to use adequate contraception. Adequate acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
• An intrauterine device with a documented failure rate of less than 1% per year.
• Vasectomized partner who is sterile prior to the female subject?s entry and is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.

Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide edify eligible disease(s)/stage(s)

Exclusion Criteria:

• History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, early-stage bladder cancer, or low-grade endometrial cancer
• Clinically significant gastrointestinal abnormalities that may affect absorption of the investigational product
• Presence of uncontrolled infection
• Prolongation of corrected QT interval (QTc) > 480 milliseconds. On antiarrhythmics or medications known to prolong QT interval
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery by-pass graft surgery
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
• History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture
• Evidence of active bleeding or bleeding diathesis.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to procedures.
• Patients on strong CYP3A4 inhibitors
• Uncorrected abnormal electrolytes- K, Mg and Ca
• Treatment with any of the following anti-cancer therapies:
• o radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
• o chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib arm	Drug: Pazopanib; 800 mg; PO; Other Names: Votrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-progression Rate Based on RECIST 1.0 Criteria (CR+PR+SD)	4-mo non-progression rate "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Per Choi Criteria	Response per Choi criteria; Complete response - Disappearance of all lesions; no new lesion; Partial response - A decrease in size of > or = 10% or a decrease in tumor density (HU) > or = 15% on CT. No new lesions. No obvious progression of nonmeasurable disease.; Stable disease - Does not meet the criteria for CR, PR, or PD. No symptomatic deterioration attributed to tumor progression.; Progressive disease - An increase in tumor size of > or = 10% and does not meet criteria of PR by tumor density (HU) on CT. New lesions. New intratumoral nodules or increase in the size of the existing intratumoral nodules.	6 months

Collaborators and Investigators

• Sponsor: Kristen Ganjoo
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Kristen N. Ganjoo, Stanford University

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: IRB-20636; RR2002/00017/09 (Other Identifier: GlaxoSmithKline); 11-311 (Other Identifier: Stanford IRB alternate); GIST0003 (Other Identifier: OnCore)