Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
Pazopanib is a drug that inhibits proteins thought to be important for new blood vessel formation. This drug has been used in other cancer research studies and information from those studies suggests that pazopanib may help block proteins that are important for the growth, invasion, and spread of cancer cells.

Detailed Description
-----------------
OBJECTIVES: Primary - To determine the progression-free survival rate in participants with relapsed or refractory small cell lung cancer who have received one prior regimen of systemic chemotherapy at 8 weeks Secondary To determine the response rate (as measured by RECIST 1.1 criteria and changes in blood flow/perfusion as measured by perfusion CT) To determine median and overall survival To characterize the toxicity profile of pazopanib in this patient population. Exploratory To analyze levels of circulating biomarkers from blood and urine samples obtained serially throughout the study and assess the utility of individual or subsets of these proteins to serve as a surrogate marker for treatment effect, treatment efficacy, and for tumor progression To measure and investigate the use of monocytes as surrogate markers of angiogenesis inhibition To analyze the subject population by identification of intra-tumoral biomarkers (such as c-kit, VEGF receptors, and microvessel density measured in available tumor biopsies) associated with the efficacy, safety and resistance to pazopanib To assess the utility of perfusion CT scan in evaluating changes in anti-angiogenic activity as a measure of treatment efficacy STATISTICAL DESIGN: This study uses a two-stage design to evaluate efficacy of cetuximab based on progression-free rate (PFR) at week 8 defined as complete response (CR), partial response (PR) or stable disease (SD) per RECIST 1.1 criteria. The null and alternative PFR are 30% and 50%. If fewer than 4 patients enrolled in the stage one cohort (n=15 patients) achieve SD or better than accrual would not proceed to stage two (n=15 patients). If 13 or more patients are progression-free of the 30 patients then the null hypothesis will be rejected. The probability that the treatment will be considered promising if the true PFR rate was 30% is 8.4% and 82% if the true PFR rate was 50%.

Official Title
-----------------
A Phase II Study of Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)

Conditions
-----------------
Small Cell Lung Cancer, Lung Cancer, SCLC

Intervention / Treatment
-----------------
* Drug: Pazopanib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of small cell neuroendocrine carcinoma based on either histology or cytology with radiologically-confirmed progressive disease. Participants should have received first-line chemotherapy and may have had up to two prior chemotherapy regimens. Radiation therapy may have been part of the permitted prior therapy. Participants with brain metastases will be allowed if they have been treated with surgery and/or radiation therapy more than 21 days prior, are asymptomatic, and are stable for at least one week off steroids. 18 years of age or older ECOG Performance status of 0, 1 or 2 Ability to swallow and retain oral medication Disease must be measurable according to RECIST 1.1 Adequate organ function as defined in the protocol Exclusion Criteria: Prior malignancy except for participants that have been disease-free for 3 years or with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for one week prior to first dose of study drug. Clinically significant gastrointestinal abnormalities Presence of uncontrolled infection Prolongation of corrected QT interval (QTc) > 480msecs History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting; myocardial infarction; unstable angina; symptomatic peripheral vascular disease; Class III or IV congestive heart failure Poorly controlled hypertension History of cerebrovascular accident including transient ischemic attack, pulmonary embolism or insufficiently treated deep venous thrombosis 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 or ulcer Evidence of active bleeding or bleeding diathesis Hemoptysis in excess of 2.5mL within 6 weeks of first dose of study drug 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 study procedures Use of any prohibited medication within the timeframes listed in the protocol Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib<br>Pazopanib was given at a dose of 800 mg orally once per day for 28 day cycles (+/- 3 days). Patients received treatment as long as they were receiving clinical benefit. | Drug: Pazopanib<br> <br> * Other names: Votrient;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 8-Week Progression-Free Rate | The 8-week progression free rate (PFR) was defined as achieving complete response (CR), partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria by the time of the first disease assessment (8 weeks). Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions; PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD; and SD is neither sufficient decrease to qualify as PR nor sufficient increase to qualify as progressive disease (PD). PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. Response needed confirmation within 4 weeks. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions. | For this endpoint, disease was evaluated radiologically at baseline and week 8 on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-20). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better objective response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. | Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-20). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pazopanib