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Adult LiposarcomaPhase 2NCT02357810

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

A Phase 2 study testing Pazopanib Hydrochloride, Oral Topotecan Hydrochloride and Laboratory Biomarker Analysis in people with Adult Liposarcoma and Metastatic Liposarcoma, run by Northwestern University at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pazopanib Hydrochloride, Oral Topotecan Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
178 participants
Where
8 sitesUnited States
Study dates
21 Mar 2015to 12 Oct 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 29Show fewer
  • 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

Who cannot join

  • 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)
Show all 47Show fewer
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Northwestern University- Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Pazopanib Hydrochloride, Oral Topotecan Hydrochloride, Laboratory Biomarker Analysis
Medical subject headings
Liposarcoma, Osteosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pazopanib HydrochlorideDrug

    Also called GW786034B, Votrient

    Given PO

  • Oral Topotecan HydrochlorideDrug

    Also called Hycamtin Capsules, Oral Hycamtin

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02357810
Study groupRoleWhat they receive
Treatment (pazopanib hydrochloride, topotecan hydrochloride)ExperimentalPatients 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.
Receives: Drug: Pazopanib Hydrochloride; Drug: Oral Topotecan Hydrochloride; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival at 12 Weeks for Patients With Soft Tissue Sarcoma (STS) Treated With Pazopanib and Oral Topotecan

    PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1 and measured at 12 weeks after treatment initiation for patients with STS. PFS estimates will be calculated using Kaplan-Meier methods

    Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.

    Measured: At 12 weeks from treatment initiation

Secondary outcomes (7)

  1. Overall Response Rate (ORR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

    ORR is defined as the percentage of patients with Complete Response (CR) plus those with Partial Response (PR) as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients best response to treatment will be used in ORR.

    Complete Response - Disappearance of all target and non target lesions Partial Response - At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD

    Measured: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.

  2. Clinical Benefit Rate (CBR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

    CBR is defined as the percentage of patients with Complete Response (CR) plus those with Partial Response (PR) plus those with Stable Disease (SD) as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients best response to treatment will be used in CBR where, in general the following definitions are used:

    Complete Response - Disappearance of all target and non target lesions Partial Response - At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.

    Measured: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.

  3. Overall Survival (OS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

    OS will be defined from start of study until death from any cause and estimates will be calculated using Kaplan-Meier methods. At time of Kaplan-meier calculations patients included the analysis who have not experienced the event will be censored at the last date of documentation of survival status.

    Measured: During treatment where one cycle = 28 days and range of cycles completed by patients 1-33, then for 2 years (for patients with progression) and 5 years (for patients without progression) following discontinuation of treatment

  4. Number of Patients With Significant Adverse Events, Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03

    Toxicities will be tabulated and summarized by the number of patients experiencing each toxicity at grade 3 or grade 4

    Measured: From treatment initiation until 30 days post last treatment, at the beginning of each cycle where 1 cycle=28 days. Range of cycles completed by patients 1-33 cycles

  5. Median Progression Free Survival (PFS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.

    PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients included in the analysis, who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free.

    Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.

    Measured: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. And then for up to 5 years post treatment discontinuation.

  6. Progression Free Survival in Patients With Osteosarcoma Treated With Combination Pazopanib and Topotecan.

    PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients included in the analysis, who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free.

    Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.

    Measured: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. Then for up to 5 years post treatment discontinuation

  7. Progression Free Survival for Patients With Liposarcoma Treated With Combination Pazopanib and Topotecan.

    PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free.

    Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.

    Measured: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. Then up to 5 years post treatment discontinuation.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2015 (estimated)
  2. Study start21 Mar 2015
  3. Primary completion27 Apr 2018
  4. Study completion12 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
178 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02357810
Sponsor's protocol ID
NU 14S03
Other IDs
NCI-2014-02583, STU00200112, NU 14S03, P30CA060553
Status last verified
May 2022
First submitted
3 Feb 2015
Last updated
7 Jun 2022
Data monitoring committee
Yes

Publications

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib Hydrochloride, Oral Topotecan Hydrochloride and Laboratory Biomarker Analysis in people with Adult Liposarcoma and Metastatic Liposarcoma, run by Northwestern University at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival at 12 Weeks for Patients With Soft Tissue Sarcoma (STS) Treated With Pazopanib and Oral Topotecan (time frame: At 12 weeks from treatment initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02357810, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.

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