Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborators:
Massachusetts General Hospital
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
GlaxoSmithKline
Information provided by (Responsible Party):
Leena Gandhi, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01253369
First received: November 17, 2010
Last updated: December 8, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Small Cell Lung Cancer
Lung Cancer
SCLC
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 8-Week Progression-Free Rate [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.


Enrollment: 33
Study Start Date: June 2010
Study Completion Date: December 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib
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
Other Name: Votrient

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%.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253369

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
GlaxoSmithKline
Investigators
Principal Investigator: Leena Gandhi, MD, PhD Dana-Farber Cancer Institute
  More Information

Publications:
Gandhi L; Heist RS; Lucca JV; Temel JS; Fidias P; Morse LK; Johnson BE; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA. A phase II trial of pazopanib in relapsed/refractory small cell lung cancer (SCLC). J Clin Oncol 2012; 30 (suppl; abstr 7099)

Responsible Party: Leena Gandhi, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01253369     History of Changes
Other Study ID Numbers: 10-125  113115 
Study First Received: November 17, 2010
Results First Received: December 8, 2015
Last Updated: December 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
pazopanib

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms

ClinicalTrials.gov processed this record on August 25, 2016