Clinical trial NCT01759303: Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung
Official title: A Phase II Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteosarcoma
Metastatic Osteosarcoma
Lead sponsor: George Clinical Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2013-01-03
Enrollment: 12
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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
* 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.

Exclusion Criteria:

* 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.
* Hemoptysis of red blood 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.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that contraindicates participation.
* An untreated tumor growth rate of \< 6.1% during the Screening period may exclude some patients.

Primary outcomes:
measure: 4-month Progression Free Survival (PFS) per RECIST version 1.1 guidelines
timeFrame: 4 months from the beginning of study treatment
Secondary outcomes:
measure: 4-month PFS per WHO criteria
timeFrame: 4 months from the beginning of study treatment
measure: Pharmacokinetics evaluation
timeFrame: Day 1 of Cycles 2 and 3 (Approximately 5 and 7 weeks from the start of study treatment)
measure: Tumor growth kinetics
timeFrame: 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
measure: Response rate per RECIST version 1.1
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: Cycle 1 Day 1 (start of study treatment) up to death or 60 months after the end of study treatment, whichever occurs first
measure: PFS
timeFrame: 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
measure: Response rate per WHO criteria
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital/Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: City of Hope Medical Center
name: Warren A Chow, MD
role: STUDY_CHAIR
References:
citation: 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.