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

Gastrointestinal Stromal Tumor (GIST) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01391611
• Other study ID #: GIST0003
• Secondary ID: RR2002/00017/092
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 8, 2011
• Last updated: December 12, 2012
• Start date: July 2011
• Est. completion date: December 2013

Study information

• Verified date: December 2012
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor (GIST)
• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Pazopanib
800 mg; PO

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Kristen Ganjoo	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-progression rate based on RECIST criteria (CR+PR+SD)		2 years	Yes
Secondary	Response per Choi criteria		6 months	No