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

NCT01759303 | Terminated Phase 2

• 1 other identifier: AWACMOS1102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Osteosarcoma; Metastatic Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• 4-month Progression Free Survival (PFS) per RECIST version 1.1 guidelines

  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.

  4 months from the beginning of study treatment

Secondary Outcomes (7)

• 4-month PFS per WHO criteria

  4 months from the beginning of study treatment

• Pharmacokinetics evaluation

  Day 1 of Cycles 2 and 3 (Approximately 5 and 7 weeks from the start of study treatment)

• Tumor growth kinetics

  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

• Response rate per RECIST version 1.1

  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

• Overall Survival (OS)

  Cycle 1 Day 1 (start of study treatment) up to death or 60 months after the end of study treatment, whichever occurs first

Study Arms (1)

pazopanib

EXPERIMENTAL

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

Interventions

pazopanib DRUG

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.

Also known as: Votrient

pazopanib

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Measurable disease per Response Evaluation Criteria in Solid Tumors (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 lower limit of normal 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.

You may not qualify if:

• Children not in the care or custody of a biological parent, adoptive parent, appointed legal guardian, or legally appointed foster 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.

Sponsors & Collaborators

• Emerald Clinical Inc.: lead
• Novartis: collaborator

Study Sites (4)

City of Hope

Duarte, California, 91010, United States

Location

Massachusetts General Hospital/Dana Farber Cancer Institute

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Frankel P, Ruel C, Uche A, Choy E, Okuno S, Somiah N, Chow WA. Pazopanib in Patients with Osteosarcoma Metastatic to the Lung: Phase 2 Study Results and the Lessons for Tumor Measurement. J Oncol. 2022 Jan 15;2022:3691025. doi: 10.1155/2022/3691025. eCollection 2022.

  PMID: 35075361 DERIVED

MeSH Terms

Conditions

Osteosarcoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Warren A Chow, MD

  City of Hope Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2012
• First Posted: January 3, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: May 1, 2017
• Last Updated: April 13, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)