Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by ACORN Research, LLC
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ACORN Research, LLC
ClinicalTrials.gov Identifier:
NCT01759303
First received: December 21, 2012
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine the 4-month Progression-Free Survival (PFS), with demonstrated increase in tumor doubling time, of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines.


Condition Intervention Phase
Osteosarcoma
Metastatic Osteosarcoma
Drug: pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung

Resource links provided by NLM:


Further study details as provided by ACORN Research, LLC:

Primary Outcome Measures:
  • 4-month Progression Free Survival (PFS) per RECIST version 1.1 guidelines [ Time Frame: 4 months from the beginning of study treatment ] [ Designated as safety issue: No ]

    The primary objective of the study is to evaluate the 4-month PFS (with demonstrated increase in tumor doubling time) of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines.

    Tumor growth rate will be calculated by measuring growth at the specified intervals for the single, longest dimension of the tumor(s) (RECIST) and by calculating the area of the tumor(s), which will be the product of the longest dimension of the tumor(s) multiplied by its longest, perpendicular dimension (WHO).

    Progressive disease (PD) for target lesions is defined as at least a 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions. Unequivocal progression of existing non-target lesions.



Secondary Outcome Measures:
  • 4-month PFS per WHO criteria [ Time Frame: 4 months from the beginning of study treatment ] [ Designated as safety issue: No ]
    The primary objective of the study is to evaluate the 4-month PFS (with demonstrated increase in tumor doubling time) of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines. The study statistician will calculate tumor growth rate per WHO criteria based on bidimensional tumor measurements (i.e., longest dimension of the tumor(s) and its longest perpendicular dimension) at each imaging time point.

  • Pharmacokinetics evaluation [ Time Frame: Day 1 of Cycles 2 and 3 (Approximately 5 and 7 weeks from the start of study treatment) ] [ Designated as safety issue: No ]
    Evaluate the pharmacokinetics of pazopanib to define correlation of minimal drug concentrations with PFS, RR, duration of response, OS, and safety. Samples will be collected on Day 1 of Cycles 2 and 3 for plasma pazopanib trough PKs to assess the population of subjects with concentration greater than the target of 15 µg/mL.

  • Tumor growth kinetics [ Time Frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first ] [ Designated as safety issue: No ]
    Evaluate the tumor growth kinetics, both within subject, and across subjects over time and the change associated with pazopanib. Examine the correlation between tumor growth kinetics with pazopanib pharmacokinetics.

  • Response rate per RECIST version 1.1 [ Time Frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first ] [ Designated as safety issue: No ]
    Response rate (RR), where response is defined as complete response (CR) or partial response (PR) according to RECIST version 1.1 guidelines.

  • Overall Survival (OS) [ Time Frame: Cycle 1 Day 1 (start of study treatment) up to death or 60 months after the end of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
    The time origin for OS will be Cycle 1, Day 1. Subjects will be followed for up to 24 months after the end of treatment or until death, lost to follow-up, or withdrawal of consent, whichever occurs first.

  • PFS [ Time Frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first ] [ Designated as safety issue: No ]
    The time origin for PFS will be Cycle 1, Day 1. Repeat radiological imaging will be conducted after every 2 cycles of treatment (approximately 8 weeks)to evaluate disease status per RECIST v.1.1 and WHO criteria. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 60 months.

  • Response rate per WHO criteria [ Time Frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first ] [ Designated as safety issue: No ]
    Response rate (RR), where response is defined as complete response (CR) or partial response (PR) per WHO criteria.


Estimated Enrollment: 35
Study Start Date: April 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pazopanib

For subjects > 18 years of age and subjects 16-17 years of age with a BSA ≥ 1.6 Pazopanib 800mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity.

For subjects 16-17 years of age with a BSA < 1.6 m2, Pazopanib 600mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity.

Drug: pazopanib

For subjects > 18 years of age and subjects 16-17 years of age with a BSA ≥ 1.6 Pazopanib 800mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity.

For subjects 16-17 years of age with a BSA < 1.6 m2, Pazopanib 600mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity.

Other Name: Votrient

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent or assent
  • Age > or = to 16 years
  • Histologically confirmed diagnosis of osteosarcoma with lung metastasis, who have progressed on the prior line of therapy, or relapsed
  • Ineligible for curative pulmonary metastasectomy
  • ECOG performance status of 0-2
  • Measurable disease per RECIST version 1.1 guidelines. At least one measurable lesion must be in the lungs.
  • Eligible subjects are required to have > or = to 1 line of multi-agent chemotherapy either neoadjuvantly or adjuvantly. Subjects may have had 0-2 lines of therapy for metastatic disease.
  • Measured cardiac ejection fraction > or = to 50% or the institutional LLN by echocardiogram or MUGA scan.
  • Adequate organ system function.
  • Females must be either non-child bearing potential or have a negative pregnancy test within 3 to 5 days prior to the first dose of study drug.

Exclusion Criteria:

  • Children in care.
  • Prior exposure to VEGFR tyrosine kinase inhibitor (small molecule or antibody) or VEGFR antibody.
  • Prior malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
  • History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.
  • Presence of uncontrolled infection.
  • Corrected QT interval (QTc) > 480 msecs using Bazett's formula.
  • History of certain cardiovascular conditions within the past 6 months.
  • Class II-IV congestive heart failure, as defined by the New York Heart Association
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Prior major surgery or trauma within 28 days prior to the protocol-mandated 4-week drug holiday and/or presence of any non-healing wound, fracture, or ulcer.
  • Evidence of active bleeding or bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
  • Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 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/assent, or compliance to study procedures.
  • Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug, whichever is longer, prior to the first dose of study drug and for the duration of the study treatment.
  • Radiation therapy, minor surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days prior to the protocol-mandated 4-week drug holiday.
  • Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to the protocol-mandated 4-week drug holiday.
  • Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.
  • An untreated tumor growth rate of < 6.1% during the Screening period may exclude some patients.
  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: NCT01759303

Contacts
Contact: Stacey Stephenson (901) 435-5574 sstephenson@acorncro.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Julie Kilpatrick, RN, MSN    626-256-4673 ext 61457    jkilpatrick@coh.org   
Principal Investigator: Warren Chow, MD         
United States, Massachusetts
Massachusetts General Hospital/Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Contact: Diane Gaucher, RN    617-643-2427    dlgaucher@partners.org   
Principal Investigator: Edwin Choy, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact    507-538-7623      
Principal Investigator: Scott Okuno, MD         
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates Recruiting
Philadelphia, Pennsylvania, United States, 19106
Contact: Holly Kilpatrick    215-829-6117    Holly.kilpatrick@uphs.upenn.edu   
Principal Investigator: Lee Hartner, MD         
Sponsors and Collaborators
ACORN Research, LLC
GlaxoSmithKline
Investigators
Study Chair: Warren A Chow, MD Beckman Research Institute
Study Chair: Arthur P Staddon, MD Pennsylvania Oncology Hematology Associates
  More Information

No publications provided

Responsible Party: ACORN Research, LLC
ClinicalTrials.gov Identifier: NCT01759303     History of Changes
Other Study ID Numbers: ACORN AWACMOS1102
Study First Received: December 21, 2012
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma

ClinicalTrials.gov processed this record on July 28, 2014