Trial of Pazopanib in Patients With Solitary Fibrous Tumor and Extraskeletal Myxoid Chondrosarcoma

March 24, 2023 updated by: Grupo Espanol de Investigacion en Sarcomas

A Phase II Open-Label Trial of Pazopanib Administered as a Single Agent in Patients With Unresectable or Metastatic Solitary Fibrous Tumor (SFT) and Extraskeletal Myxoid Chondrosarcoma (EMC)

Phase II, open-label, non-randomized, international multicenter clinical trial with two strata (SFT and EMC). 8 sites in Spain, 5 sites in Italy and 5 sites in France. Patients will receive oral pazopanib at 800 mg once daily continuously. Patients will continue to receive treatment until there is evidence of progressive disease, unacceptable toxicity, non-compliance, withdrawn consent or investigator decision. The main goal is to determine the objective response rate (ORR) (confirmed complete response [CR] and partial response [PR]) in patients with unresectable, locally advanced or metastatic solitary fibrous tumor and extraskeletal myxoid chondrosarcoma, using Choi and RECIST 1.1 criteria respectively.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To estimate the sample size for stratum 1 (SFT), a Simon's optimal 2-stage phase II design has been used, having considered the published response rate based on Choi criteria in SFT patients which correspond to 40% in monotherapy. For a design with P0=0.40, P1=0.60; α=0.1 and β=0.1. At the first stage, 18 patients should be enrolled into the study, if there are fewer than 8 responses (7 or less) the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. At the second stage, another 28 patients (total 46 patients) would be enrolled into the study. To reject the null hypothesis for the SFT stratum 23 responses or more (Choi criteria), out of the 46 patients, are needed.

To estimate the simple size for stratum 2 (EMC), a Simon's optimal 2-stage phase II design has been used, having considered the very scarce published information on response rate based on RECIST criteria. For a design with P0= 0.05, P1= 0.25, α=0.1 and β=0.1. At the first stage, 9 patients should be enrolled into the study, if there are not responses the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. If there is at least 1 response in this first stage, the trial will be continued and at the second stage, another 15 patients (total 24 patients) would be enrolled into the study. To reject the null hypothesis for the EMC stratum 3 responses or more (RECIST criteria), out of the 24 patients, are needed.

For variables that follow binomial distributions (e.g. response rate) frequency and percentages will be calculated, together with their corresponding exact 95% confidence intervals. For time-to-event variables (e.g. PFS or OS) Kaplan-Meier estimations will be used. To analyze the reduction of risk and the influence of other variables on time-to-event variables Cox Regression will be applied. To correlate pharmacodynamics markers and biomarkers with clinical response standard methods for bivariate and multivariate regression and correlation will be used.

Study Type

Interventional

Enrollment (Actual)

96

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
        • Hospital De La Santa Creu I Sant Pau
      • Madrid, Spain
        • Hospital Ramón y Cajal
      • Madrid, Spain
        • Hospital La Paz
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Zaragoza, Spain
        • H. Miguel Servet
    • Islas Baleares
      • Palma De Mallorca, Islas Baleares, Spain
        • H. Son Espases
    • Santa Cruz De Tenerife
      • Tenerife, Santa Cruz De Tenerife, Spain, 38320
        • H. Universitario de Canarias

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
  • Age ≥ 18 years or legal age of consent if greater than 18 years.
  • Histologic diagnosis of solitary fibrous tumor (stratum 1) or extraskeletal myxoid chondrosarcoma (stratum 2) (unresectable, locally advanced or metastatic disease) confirmed by central pathology review.
  • Patients with metastatic tumor suitable for complete resection can be recruited. In absence of progressive disease these patients should be treated with the study drug for at least 6 months.
  • For patients who have received previous anticancer treatments, progressive disease must be demonstrated within 6 months prior to enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Measurable disease according to Choi (SFT) and RECIST 1.1 (EMC) criteria.
  • Patients could have received a maximum of 4 lines of chemotherapy for metastatic disease prior to trial enrollment.
  • Patients must be able to swallow and retain the study drug.
  • Adequate organ system function as defined in protocol.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment. All patients (both male and female) must agree to use effective contraception methods, as defined in the protocol.
  • Left ventricular ejection fraction (LVEF) above the lower limit of normal for the institution, either by echocardiogram or MUGA.
  • Patients in France will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Prior malignancy, except patients who have had another malignancy and have been disease-free for 10 years, or those with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
  • Central nervous system metastases at baseline, with the exception of patients who have previously-treated central nervous system metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6-month time interval.
  • Patients who have received previous antiangiogenic agents.
  • Significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
  • Significant gastrointestinal abnormalities that may affect absorption of investigational product.
  • Corrected QT interval (QTc) > 480 msecs.
  • History of any one or more of the following cardiovascular conditions within the past 6 months:

Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class II, 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].
  • History of cerebrovascular accident.
  • 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 (catheter placement and similar procedures are 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.
  • Recent hemoptysis (>=½ teaspoon 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 prohibited medications listed in the protocol for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  • Treatment with any of the following anti-cancer therapies:

Radiation therapy, surgery or tumor embolization within 28 days prior to the first dose of pazoapnib or 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 pazopanib

  • Administration of any non-oncologic drug within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment.
  • Ongoing toxicity from prior anti-cancer therapy that is >Grade 1 (except anemia, see Table 1 above) and/or that is progressing in severity, except alopecia.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pazopanib
Single arm of pazopanib 800 mg (2x400 mg or 4x200 mg) given as a single agent once daily continuously.
Drug: Pazopanib
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.
Other Names:
  • Votrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 48 weeks
Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR]), measured using Choi and RECIST 1.1 criteria. Response criteria will be based on the baseline identification of target lesions and follow-up until tumor progression.
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of pazopanib
Time Frame: 48 weeks
Efficacy measured by the progression-free survival (PFS) rate assessed by median time
48 weeks
Overall survival (OS)
Time Frame: 72 weeks
Overall survival (OS) measured since treatment start date until date of death, whichever the cause
72 weeks
Clinical benefit rate (CBR)
Time Frame: 48 weeks
Clinical benefit rate (CBR). Patients who have reached CR, PR or SD during 6 months or more, presenting clinical improvement of symptoms, will be considered as having experienced clinical benefit.
48 weeks
Long term safety profile of pazopanib
Time Frame: 48 weeks
Long term safety profile of pazopanib, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Espanol de Investigacion en Sarcomas

Investigators

  • Principal Investigator: Andrés Redondo, MD, Hospital La Paz
  • Study Director: Josefina Cruz, MD, Hospital Universitario de Canarias
  • Study Director: Javier Martín, MD, Hospital Son Espases
  • Principal Investigator: Antonio López-Pousa, MD, Hospital Sant Pau
  • Principal Investigator: M. Ángeles Vaz, MD, Hospital Universitario Ramón y Cajal
  • Principal Investigator: Javier Martínez-Trufero, MD, Hospital Miguel Servet
  • Principal Investigator: Pilar Blay, MD, Hospital Central de Asturias
  • Principal Investigator: Pilar Sancho, MD, Hospital Virgen del Rocío
  • Principal Investigator: Jean Yves Blay, MD, Centre léon bérard
  • Study Director: Silvia Stacchiotti, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2014

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

March 24, 2023

Study Registration Dates

First Submitted

February 14, 2014

First Submitted That Met QC Criteria

February 17, 2014

First Posted (Estimate)

February 19, 2014

Study Record Updates

Last Update Posted (Actual)

March 27, 2023

Last Update Submitted That Met QC Criteria

March 24, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEIS-32
  • 2013-005456-15 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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