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Pazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas

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ClinicalTrials.gov Identifier: NCT02357810
Recruitment Status : Recruiting
First Posted : February 6, 2015
Last Update Posted : October 1, 2018
Sponsor:
Collaborators:
GlaxoSmithKline
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

February 3, 2015
February 6, 2015
October 1, 2018
February 2015
July 2019   (Final data collection date for primary outcome measure)
Time from enrollment to progression [ Time Frame: At 12 weeks ]
Progression defined as changes in RECIST 1.1 defined imaging, progression in non-target lesions as defined by RECIST 1.1, unequivocal clinical deterioration, or death from any cause. Will be estimated for each histologic group (STS, osteoscaroma, and liposarcoma) using Kaplan-Meier methods.
Same as current
Complete list of historical versions of study NCT02357810 on ClinicalTrials.gov Archive Site
  • Overall response rate (CR + PR) per RECIST version 1.1 [ Time Frame: Up to 5 years ]
    Response rates will be summarized by the observed proportion of patients with response, along with a 95% confidence interval.
  • Clinical benefit (CR+ PR + SD) per RECIST version 1.1 [ Time Frame: Up to 5 years ]
    Response rates will be summarized by the observed proportion of patients with response, along with a 95% confidence interval.
  • OS [ Time Frame: Time from the first dose of the study treatment until death from any cause, assessed up to 2 years ]
    Will be estimated for each histologic group (STS, osteoscaroma, and liposarcoma) using Kaplan-Meier methods.
  • Incidence of adverse events, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 30 days post-treatment ]
    Toxicities will be tabulated and summarized by the number of patients experiencing each toxicity.
Same as current
Change in cytokine levels [ Time Frame: Baseline to 12 weeks ]
Verification of results of Sleijfer et al and to determine if there is an even earlier correlation that can be detected between levels of these cytokines and PFR as well as OS which may allow us to better predict treatment response early on in therapy.
Same as current
 
Pazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas
A Phase II Study of Pazopanib With Oral Topotecan in Patients With Metastatic and Non-resectable Soft Tissue and Bone Sarcomas
The purpose of this clinical research study is to learn if pazopanib when given in combination with topotecan can help to control sarcomas. The safety of this drug combination will also be studied. Pazopanib hydrochloride and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine progression free rate at week 12 for patients with soft tissue sarcoma (STS) treated with pazopanib (pazopanib hydrochloride) plus oral topotecan (topotecan hydrochloride).

SECONDARY OBJECTIVES:

I. To determine the overall response rate for patients with STS treated with combination pazopanib and topotecan.

II. To determine the clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) for patients with STS treated with combination pazopanib and topotecan.

III. To determine median progression-free rate (PFR) for patients with STS treated with combination pazopanib and topotecan.

IV. To evaluate overall survival (OS) for patients with STS treated with combination pazopanib and topotecan.

V. To assess safety and tolerability for patients treated with combination pazopanib and topotecan.

VI. To estimate the PFR for patients with osteosarcoma treated with combination pazopanib and topotecan.

VII. To estimate the PFR for patients with liposarcoma treated with combination pazopanib and topotecan.

TERTIARY OBJECTIVES:

I. To estimate the correlation of PFR and OS to levels of soluble vascular endothelial growth factor receptor 2 (sVEGFR2) and phosphatidylinositol-glycan biosynthesis class F (PIGF).

OUTLINE:

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 and topotecan hydrochloride PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or until discontinuation per patient preference or physician recommendation.

After completion of study treatment, patients are followed up every 6 months for 2 or 5 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adult Liposarcoma
  • Metastatic Liposarcoma
  • Metastatic Osteosarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Liposarcoma
  • Recurrent Osteosarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Drug: Pazopanib Hydrochloride
    Given PO
    Other Names:
    • GW786034B
    • Votrient
  • Drug: Oral Topotecan Hydrochloride
    Given PO
    Other Names:
    • Hycamtin Capsules
    • Oral Hycamtin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (pazopanib hydrochloride, topotecan hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28 and topotecan hydrochloride PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Pazopanib Hydrochloride
  • Drug: Oral Topotecan Hydrochloride
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
136
Same as current
June 2020
July 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up
  • Patients must have a histologically confirmed diagnosis of:

    • Metastatic soft tissue sarcomas (non-liposarcoma)
    • Metastatic osteosarcoma
    • Metastatic liposarcoma- high grade, de-differentiated, or myxoid Note: pathology is not required to be reviewed at the treating institution; a copy of the pathology report is sufficient for eligibility purposes
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients must have measurable disease within 4 weeks prior to registration by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10mm with spiral computed tomography (CT) scan
  • Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease; it will be up to the investigator to determine what constitutes a "regimen" in each case; the last dose of systemic therapy much have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose at least 6 weeks prior to initiation of therapy
  • Patients with brain metastasis are eligible for participation only if they have been treated with definitive surgery or radiation (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 12 week interval
  • Absolute neutrophil count (ANC) >= 1.5 X 10^9/L (tested within 7 days prior to Registration)
  • Hemoglobin >= 9 g/dL (5.6 mmol/L)

    • Subjects may not have had a transfusion within 7 days of screening assessment
  • Platelets >= 100 X 10^9/L

    • Subjects may not have had a transfusion within 7 days of screening assessment
  • Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 X upper limit of normal (ULN)

    • Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
  • Activated partial thromboplastin time (aPTT) =< 1.2 X ULN
  • Total bilirubin =< 1.5 X ULN
  • Alanine amino transferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN

    • Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted
  • Serum creatinine =< 1.5 mg/dL (133 umol/L) or, if > 1.5 mg/dL: calculated creatinine clearance (ClCR) >= 30 mL/min to >= 50 mL/min
  • Urine protein to creatinine ratio (UPC) < 1

    • If UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
  • Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; Note: a FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy
    • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must have a negative pregnancy test within 7 days prior to registration on study

    • Note: female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug
  • Are able to swallow and retain oral tablets

Exclusion Criteria:

  • Patients with any of the following sarcoma histologic subtypes will not be eligible for participation:

    • Alveolar soft-part sarcoma
    • Chondrosarcoma
    • Dermatofibrosarcoma
    • Ewing sarcoma
    • Gastrointestinal stromal tumor (GIST)
    • Kaposi sarcoma (non-human immunodeficiency virus [HIV] and HIV related disease)
    • Mixed mesodermal tumor/carcinosarcoma
    • Low grade (grade 1) sarcomas
    • Rhabdomyosarcoma (embryonal, alveolar, pleomorphic)
    • Interdigitating dendritic sarcoma
    • Giant cell tumor of the bone
  • Patients must not have received prior treatment with pazopanib or topotecan
  • Patients must not have an active secondary malignancy
  • Prior malignancy, unless they have been disease-free for 3 years, or have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

    • Active peptic ulcer disease
    • Known intraluminal metastatic lesion/s with risk of bleeding
    • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel
  • Corrected QT interval (QTc) > 480 msecs using Bazett's formula
  • History of any one or more of the following cardiovascular conditions within the past 12 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Coronary artery bypass graft surgery
    • Symptomatic peripheral vascular disease
    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals; at least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement; these three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure; the mean SBP / DBP ratio must be < 140/90 mmHg (or 150/90 mm Hg, if this criterion deemed safe by principal investigator [PI] and the quality assurance monitor [QAM]) in order for a patient to be eligible for the study
  • Patients with a history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism, or untreated deep venous thrombosis (DVT); patients with DVT must have received appropriate therapy for at least 6 months to be considered eligible
  • Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery)
  • Evidence of active bleeding or bleeding diathesis
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage

    • Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed
    • Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
  • Recent hemoptysis (>= 1/2 teaspoon [2.5 mL]) of red blood within 8 weeks before first dose of study drug
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures
  • Unable or unwilling to discontinue use of inducers and inhibitors of cytochrome P450 (CYP450) listed 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; cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications; breast cancer resistance protein (BCRP) and p-glycoprotein (PgP) inducers and inhibitors will be also prohibited
  • Treatment with any of the following anti-cancer therapies:

    • Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of therapy
    • Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of therapy
  • Administration of any non-oncologic investigational drug within 30 days or 5 half-lives whichever is longer prior to receiving the first dose of study treatment
  • Any ongoing toxicity related to prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (exceptions include alopecia, fatigue, and hematologic toxicities)
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Study Coordinator (312)695-1301 cancertrials@northwestern.edu
United States
 
 
NCT02357810
NU 14S03
NCI-2014-02583 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STU00200112
NU 14S03 ( Other Identifier: Northwestern University )
P30CA060553 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Northwestern University
Northwestern University
  • GlaxoSmithKline
  • National Cancer Institute (NCI)
Principal Investigator: Mark Agulnik Northwestern University
Northwestern University
September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP